Mesangial Cell Hyperplasia Research Articles

Effects of Ovariectomy on Kidney Injury in SDT Fatty Rats

Postmenopausal women are at a higher risk of developing diabetes, and estrogen can lower blood glucose levels. The purpose of this study was to investigate the effect of ovariectomy (OVX) on the pathology of diabetic nephropathy. Female SD rats and SDT fatty rat underwent bilateral OVX or sham treatment at 6 weeks of age, and their blood and kidneys were collected at 40 weeks of age for blood biochemical and histopathological analyses. OVX treatment resulted in a decrease in blood estradiol levels at 24 and 40 weeks of age. Histopathological analysis revealed that Sham-treated SDT fatty rats showed glomerular atrophy, adhesions, enlargement, mesangial cell proliferation, regenerated tubules, hyaline casts, Armani-Ebstein lesions, tubular dilatation, interstitial inflammatory cell infiltration, and fibrosis. OVX treatment slightly reduced glomerular atrophy and enlargement, renal tubular dilatation, and interstitial inflammatory cell infiltration, while slightly increased or exacerbated mesangial cell hyperplasia, tubular regeneration, and Armani-Ebstein lesions. The above findings suggest that SDT fatty rats are not a practical model to study postmenopausal diabetic nephropathy.

Clinical and genetic analysis of a child with Focal segmental glomerulosclerosis due to a novel variant of PLCE1 gene

To explore the genetic basis and clinical phenotype of a Chinese pedigree affected with Focal segmental glomerulosclerosis (FSGS). A male patient who was admitted to the First Affiliated Hospital of Zhengzhou University on July 26, 2018 was selected as the study subject. Clinical data of the patient was collected. Next generation sequencing and Sanger sequencing were carried out to detect the variant sites. Bioinformatic software was used to simulate the effect of candidate variant on the protein functions. Ultrasound exam of the patient showed enhanced echo for the renal parenchyma. Kidney biopsy had confirmed the pathological diagnosis of FSGS (non-specific). Electronic microscopy displayed segmental sclerosis of the glomeruli, mild hyperplasia of mesangial cells and matrix. The proband was found to harbor two novel variants of the PLCE1 gene, namely c.3199delA (p.N1067Mfs*15) and c.4441_4443delATC (p.1481_1481del), which were respectively inherited from his mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PM2_Supporting+PP3; PM2_Supporting+PM3+PP3). Bioinformatic simulation suggested that both variants could significantly affect the tertiary structure of the PLCE1 protein. The c.4441_4443delATC and c.3199delA variants of the PLCE1 gene probably underlay the pathogenesis of the FSGS in this pedigree.

Clinicopathological characteristics and outcomes of lupus nephritis patients with scanty immune depositions in kidneybiopsies.

The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear. Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models. Among 498 lupus nephritis patients, 81 were diagnosed withscanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferativefeatures at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significantrisk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients. Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients.

Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice

To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible. Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity. Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity. Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Regulatory effect of IL-38 on NF-κB pathway in systemic lupus erythematosus

BackgroundIL-38 is a newly identified cytokine that exhibits immunosuppression effects. However, there are few studies focusing on the effects and mechanisms of IL-38 in the systemic lupus erythematosus (SLE). AimWe investigated the effects and mechanisms of IL-38 on NF-κB signaling pathway in SLE. MethodsLevels of IL-38, IL-36R, IL-1RAcP, IKKα/β, NF-κB, TNF-α and anti-dsDNA antibody levels in peripheral blood of SLE patients, and in peripheral blood and kidney tissues of MRL/lpr mice, were examined with real-time PCR, ELISA, Western blot and immunohistochemistry. Pathological changes of kidney were detected with PAS staining. Recombinant human IL-38 protein and IL-38 siRNA were used to intervene the PBMCs of SLE patients and MRL/lpr mice. ResultsThe mRNA and protein levels of IL-38 in peripheral blood of SLE patients decreased and were positively correlated. The mRNA and protein levels of IKKα/β, NF-κB, and TNF-α increased, especially in patients with active SLE. There was a negative correlation between IL-38 and the levels of IKKα/β, NF-κB and TNF-α in SLE patients. In vitro experiments showed that the levels of IKKα/β, NF-κB and TNF-α, and anti-dsDNA antibodies decreased in PBMCs of SLE patients after treatment with human recombinant IL-38 protein. These effects were reversed after IL-38 siRNA intervention. Consistent results were obtained on IL-38, IKKα/β, NF-κB, and TNF-α in MRL/lpr lupus mice after treatment with IL-38 protein or IL-38 shRNA. Additionally, kidney function (reflected by creatinine and blood urea nitrogen), anti-dsDNA antibody, complement C3, and urinary protein levels decreased after treatment with IL-38 protein but increased after IL-38 shRNA treatment. PAS staining showed IL-38 protein treatment induced mild hyperplasia of glomerular mesangial cells and a small amount of lymphocyte infiltration. However, these were aggravated after IL-38 shRNA treatment. ConclusionIL-38 may be involved in the occurrence and development of SLE by regulating the NF-κB signaling pathway. This study only discussed the relationship between IL-38 and NF-κB, and more biological functions of IL-38 need to be further studied.

Autopsy findings of COVID-19 in children: a systematic review and meta-analysis.

Clinical features of COVID-19 range from mild respiratory symptoms to fatal outcomes. Autopsy findings are important for understanding COVID-19-related pathophysiology and clinical manifestations. This systematic study aims to evaluate autopsy findings in paediatric cases. We searched PubMed, EMBASE, and Cochrane Database Reviews. We included studies that reported autopsy findings in children with COVID-19. A total of 11 studies (24 subjects) were included. The mean age of patients was 5.9 ± 5.7years. Grossly, there was pericardial and pleural effusion, hepatosplenomegaly, cardiomegaly, heavy soft lung, enlarged kidney, and enlarged brain. The autopsy findings of the lungs were diffuse alveolar damage (78.3%), fibrin thrombi (43.5%), haemorrhage (30.4%), pneumonia (26%), congestion and oedema (26%), angiomatoid pattern (17.4%), and alveolar megakaryocytes (17.4%). The heart showed interstitial oedema (80%), myocardial foci of band necrosis (60%), fibrin microthrombi (60%), interstitial and perivascular inflammation (40%), and pancarditis (30%). The liver showed centrilobular congestion (60%), micro/macrovesicular steatosis (30%), and arterial/venous thrombi (20%). The kidney showed acute tubular necrosis (75%), congestion (62.5%), fibrin thrombi in glomerular capillaries (37.5%), and nephrocalcinosis, mesangial cell hyperplasia, tubular hyaline/granular casts (25% each). The spleen showed splenitis (71.4%), haemorrhage (71.4%), lymphoid hypoplasia (57.1%), and haemophagocytosis (28.6%). The brain revealed oedema (87.5%), congestion (75%), reactive microglia (62.5%), neuronal ischaemic necrosis (62.5%), meningoencephalitis (37.5%), and fibrin thrombi (25%). SARS-CoV-2 and CD68 were positive by immunohistochemistry in 85.7% and 33.3% cases, respectively. Autopsy findings of COVID-19 in children are variable in all important organs. It may help in better understanding the pathogenesis of SARS-CoV-2.

Renal ultrastructural damage induced by chronic exposure to copper oxide nanomaterials: Electron microscopy study

Copper oxide nanomaterials are used in many biomedical, agricultural, environmental, and industrial sectors with potential risk to human health and the environment. The present study was conducted to determine the renal ultrastructural damage caused by 25nm CuO nanoparticles in renal tissues. Adult healthy male Wister Albino rats (Rattus norvegicus) were administered 35 intraperitoneal injections of CuO nanoparticles (2mg/kg). Ultrastructural changes were evaluated using transmission electron microscopy techniques. The renal tissues of rats with subchronic exposure to CuO nanoparticles demonstrated glomerular alterations that included hypertrophic endothelial cells, dilated capillaries and occlusions, podocyte hypertrophy, pedicle disorganization, mesangial cell hyperplasia, and crystalloid precipitation. Moreover, the treated renal cells exhibited mitochondrial swelling and crystolysis, cytoplasmic vacoulization, lysosomal hypertrophy, apoptotic activity, endoplasmic reticulum dilatation, nuclear deformity, chromatin dissolution, and basement membrane thickening. In addition, disruption and disorganization of the renal cells microvilli together with cystolic inclusions were also detected. It was concluded from the present findings that CuO nanoparticles could interact with the components of the renal tissues in ways that could cause ultrastructural injury, suggesting renal tissue pathophysiology. Additional studies are suggested for a better understanding the nanotoxicity of CuO nanomaterials.

Segmental Arterial Mediolysis: A Multiguised Vasospastic Arteriopathy with Collateral Mesangial Cell Hyperplasia and Cardiac Toxicity Generated by Norepinephrine and Hyperdense Adrenoceptors Alone or by Crosstalk with Other Pressor Agents.

Segmental arterial mediolysis (SAM), an uncommon vasospastic arteriopathy occurring in the muscular arteries innervated by the peripheral sympathetic nervous system, usually presents with catastrophic abdominal and retroperitoneal hemorrhages in elderly patients. SAM is initiated by the coupling of norepinephrine to plastically derived hyperdense foci of alpha-1 adrenergic receptors on the sarcolemma of arterial muscle. This ligand is created by stimuli signaled by iatrogenic sympathomimetic agonists, some beta-2 agonists, or an excessive release of adrenal catecholamines. Coupling of this ligand with cytoplasmic heterotrimeric Gq protein excessively signals a cascade of biochemical events generating two principal lesions of injurious-phase SAM—the shearing of the outer media from the adventitia and an overload of cytoplasmic calcium ions toxic to mitochondria causing mediolysis and/or apoptosis. The massive hemorrhages are caused by ruptured gap aneurysms created by the transmedial loss of the medial muscle. A norepinephrine-directed reparative response rapidly develops either resolving angiographic injurious lesions or creating a body of vascular disorders, the new guises of SAM with ischemic clinical profiles. These present in the epicardial, vertebral, intestinal, and retroperitoneal arteries, often in younger females as fibromuscular dysplasia, dissecting hematomas, and persistent aneurysms. Norepinephrine can crosstalk with other pressor agents to create SAM lesions—serotonin with idiopathic pulmonary hypertension and persistent pulmonary hypertension in the newborn, histamine in spontaneous coronary artery dissections with eosinophilia, and endothelin-1 in a field effect generated by SAM that creates venous fibromuscular dysplasia. Norepinephrine also participates in the collateral development of mesangial hyperplasia with focal segmental glomerulosclerosis and myocardial mediolysis and apoptosis in subjects with markedly elevated heart rates. Conclusion. Norepinephrine coupling with plastically elevated alpha-1 adrenoceptor or other pressor agents generates SAM, a histologically recognizable vasospastic arteriopathy, that with repair is transformed into several different standardized arterial diseases that alter SAM's clinical profile from a hemorrhagic to an ischemic disorder.

The adverse effect of long term intake of Monosodium Glutamate on kidney performance

Monosodium glutamate (MSG) is a food additive that is considered as a water and environmental pollutant and affects the tissues of the living being. This study was aimed to find the effect of long-term administration of MSG on the mass of mesangial cells of the kidneys. Forty adult male rats were divided into four groups (10 each). Control groups 1&2 were supplied orally with distilled water for 30 and 60 days, respectively. Treatment groups 1&2 were supplied orally with 15 mg/kg Bwt of MSG for 30 & 60 days, respectively. Control and treatment groups were sacrificed, specimens of kidneys were obtained, fixed with 10% neutral buffered formalin, processed by Routine histological techniques, stained by Hematoxylin and eosin, and PAS (Periodic Acid-Schiff) stains then examined under the light microscope. The result found enlargement in a mesangial mass represented by hypertrophy and hyperplasia of mesangial cells leading to mesangial proliferative glomerulonephritis. Accordingly, the study showed an increase in creatinine values, indicating a disturbance in renal function. This will lead to a decrease in the sizes of the glomeruli of renal corpuscles and a relative increase of Bowman’s space. With the time of the experiment, the glomerular capillaries and gates of basement membranes will be closed, resulting in renal filtration disorders. It was concluded that the long-term intake of MSG leads to indirect narrowing of the glomerular capillary lumen, causing kidney failure.

Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy.

Modified Huangqi Chifeng decoction (MHCD) has been used to reduce proteinuria in immunoglobulin A nephropathy (IgAN) for many years. Previously, we have demonstrated its protective role in glomerular mesangial cells. Podocyte injury, another key factor associated with proteinuria in IgAN, has also attracted increasing attention. However, whether MHCD can reduce proteinuria by protecting podocytes remains unclear. The present study aimed to investigate the protective effects of MHCD against podocyte injury in a rat model of IgAN. To establish the IgAN model, rats were administered bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. MHCD in three doses or telmisartan was administered once daily for 8 weeks (n = 10 rats/group). Rats with IgAN developed proteinuria at week 6, which worsened over time until drug intervention. After drug intervention, MHCD reduced proteinuria and had no effect on liver and kidney function. Furthermore, MHCD alleviated renal pathological lesions, hyperplasia of mesangial cells, mesangial matrix expansion, and podocyte foot process fusion. Western blot analysis revealed that MHCD increased the expression of the podocyte-associated proteins nephrin and podocalyxin. Additionally, we stained podocyte nuclei with an antibody for Wilms’ tumor protein one and found that MHCD increased the podocyte number in rats with IgAN. In conclusion, these results demonstrate that MHCD attenuates proteinuria by reducing podocyte injury.

Ginkgetin alleviates high glucose-evoked mesangial cell oxidative stress injury, inflammation, and extracellular matrix (ECM) deposition in an AMPK/mTOR-mediated autophagy axis.

Diabetic nephropathy constitutes the leading cause for end-stage kidney disease. Ginkgetin is a common natural non-toxic biflavone and fulfills pleiotropic pharmacological characterizations, such as anti-inflammation and kidney injury. Nevertheless, its efficacy in diabetic nephropathy remains elusive. Here, ginkgetin exhibited little cytotoxicity in glomerular mesangial cells. Of note, ginkgetin restrained high glucose (HG)-induced mesangial cell proliferation and oxidative stress by inhibiting ROS and malonaldehyde levels, but enhancing antioxidant SOD activity. Additionally, ginkgetin suppressed HG-evoked transcript and release of inflammatory cytokine TNF-α, IL-1β, and IL-6. Concomitantly, the increased extracellular matrix (ECM) deposition in HG-treated glomerular mesangial cells was attenuated by ginkgetin via decreasing expression of collagen IV, fibronectin, and laminin. Intriguingly, ginkgetin-restored HG-impaired autophagy; whereas blocking autophagy by its inhibitor 3-MA overturned ginkgetin function against HG-evoked mesangial cell dysfunction. Mechanistically, ginkgetin-mediated AMPK/mTOR axis accounted for HG-impaired autophagy. Importantly, blockage of AMPK signaling reversed ginkgetin-restored autophagy and its protective efficacy against HG-induced dysfunction in mesangial cells. Thus, these findings highlight that ginkgetin may attenuate HG-evoked mesangial cell hyperplasia, oxidative stress, inflammation, and ECM accumulation by activating AMPk/mTOR-mediated autophagy pathway. Therefore, ginkgetin may alleviate the progression of diabetic nephropathy by regulating glomerular mesangial cell dysfunction, supporting a promising therapeutic agent against diabetic nephropathy.

Rapamycin alleviates renal damage in mice with systemic lupus erythematosus through improving immune response and function

This study aimed to explore the therapeutic effect and mechanism of rapamycin (RAPA) on systemic lupus erythematosus (SLE) in BALB/C mice induced by pristane. The mice were randomly divided into 5 groups (n = 6): control, model, saline, RAPA (1 mg/kg) and RAPA (2 mg/kg). All groups were injected with pristane except control. HE staining revealed 1 mg/kg and 2 mg/kg RAPA treatments obviously alleviated pathological changes in the kidney of SLE mice such as glomeruli enlargement, hyperplasia of mesangial cells, epithelial and endothelial cells, infiltration of inflammatory cells, and edema-like degeneration of renal tubules. Compared with control group, body weights and anti-ribosomal P-protein antibody (ARPA) level of the mice in model group and saline group decreased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody and urine protein in model group and saline group increased (P < 0.05). However, compared with model group and saline group, body weights of the mice in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group increased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody, ARPA, and urine protein in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group decreased (P < 0.05). Compared with control group, the proportion of dentritic cells (DC) in the kidney and peripheral blood decreased while the proportion of Th1, Th2 and Th17 cells in the spleen, kidney and peripheral blood increased in model group and saline group (P < 0.05). Compared with model group and saline group, 1 mg/kg and 2 mg/kg RAPA treatments boosted the proportion of DC in the kidney and peripheral blood, reduced the proportion of Th1 and Th17 cells in the spleen, kidney and peripheral blood, and lessened the proportion of Th2 cells in the kidney and peripheral blood (P < 0.05). In conclusion, RAPA alleviated renal damage in SLE mice through improving immune response and function.

Optic Disc Drusenoid Deposits with Hemifield Defects in a Patient with IgA Nephropathy - New Findings

To describe emerging new OCT and Humphrey visual field findings is the objective of the study. A previously treated 20-year old female patient for skin rashes, hematuria, and pain abdomen 8 months ago reported with visual disruption in the right eye for the last one week. Features of leukocytoclastic vasculitis on skin biopsy and glomerular mesangial cell hyperplasia on renal biopsy inferred a clinical diagnosis of IgA nephropathy. Consequently, proteinuria manifested one month after administration of prednisolone 50 mg/day tapered for 8 months, Visual acuity of 6/9 in the right eye and 6/6 in the left eye with normal color vision recorded in addition to early signs of papilledema. Classically, on OCT, hyperreflective intense echoes discovered in the optic disc, and accordingly inferior hemifield defects established predominantly in the right eye on HFA. Total leucocyte count at11720 cells/cu mm and ESR 60 mm/hr by the Wintrobe method with the presence of albumin, RBCs, and pus cells on urine analysis in addition to positive occult stool blood detection. C3, C4, and ANCA panel revealed negative results and the USG abdomen disclosed fatty liver with mesenteric nodes. In conclusion, Optic disc drusenoid deposits corresponding with hemifield visual field defects detected in the current case study is possibly the associated early fundus manifestation of IgA nephropathy.

Coreopsis tinctoria Nutt ameliorates high glucose-induced renal fibrosis and inflammation via the TGF-\u03b21/SMADS/AMPK/NF-\u03baB pathways

BackgroundCoreopsis tinctoria Nutt is an ethnomedicine widely used in Xinjiang, China. It is consumed as a herbal tea by local Uyghur people to treat high blood pressure and diarrhea. Our previous study confirmed that the ethyl acetate extract of Coreopsis tinctoria (AC) had a protective effect on diabetic nephropathy (DN) in an in vivo experiment. Here we aim to elucidate the protective mechanism of AC and marein, the main ingredient in Coreopsis tinctoria on renal fibrosis and inflammation in vitro under high glucose (HG) conditions.MethodsA HG-induced barrier dysfunction model in rat mesangial cells (HBZY-1) was established. The cells were exposed to AC and marein and/or HG for 24 h. Then, the renal protective effects of AC and marein via transforming growth factor-β1 (TGF-β1)/Smads, AMP-activated kinase protein (AMPK), and nuclear factor kappa beta (NF-κB) signaling were assessed.ResultsBoth AC and marein suppressed rat mesangial cell hyperplasia and significantly attenuated the expression of HG-disrupted fibrotic and inflammatory proteins in HBZY-1 cells. It was also confirmed that AC and marein remarkably attenuated HG-induced renal inflammation and fibrosis by regulating the AMPK, TGF-β1/Smads, and NF-κB signaling pathways.ConclusionThese results indicated that AC and marein may delay the progression of DN, at least in part, by suppressing HG-induced renal inflammation and fibrosis. Marein may be one of the bioactive compounds in AC.

Effect of echinacoside on kidney fibrosis by inhibition of TGF-β1/Smads signaling pathway in the db/db mice model of diabetic nephropathy.

Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with ECH. We also observed that ECH can improve histopathological findings in the kidneys of db/db mice, including collagen deposition, mesangial cell and mesangial matrix hyperplasia, basement membrane thickening, and podocyte reduction. Moreover, ECH inhibited the TGF-β1/Smads signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth muscle actin (α-SMA) levels, and upregulated E-cadherin level in the db/db mice model of DN. Our findings indicate that ECH has a therapeutic effect on DN, including the inhibition of renal tubular EMT and kidney fibrosis. Furthermore, ECH inhibits kidney fibrosis through regulation of the TGF-β1/Smads signaling pathway.

Segmental arterial mediolysis with mesangial cell hyperplasia; A review with supplementary comments concerning its pathogenesis

Background: Segmental arterial mediolysis (SAM) a rare arteriopathy causing massive bleeding or ischemic symptoms, is suspected of representing a vascular disease of the peripheral sympathetic nervous system. It is initiated by the supra physiological release of norepinephrine from the efferent branches of the peripheral sympathetic nerves that innervate the large and medial sized muscular arteries targeted in SAM. Recognized stimuli for this response are iatrogenic sympathomimetic agonists and some B-2 agonists. However, these stimuli were not always apparent in published cases of SAM casting doubt on this hypothesis. Methods and findings: SAM, reported in kidneys of slaughtered pigs, was believed to represent a dysfunctional development in a fight and flight response. Additionally some stenotic renal arteries described in cases of pheochromocytomas reportedly were caused by arterial spasm and fibromuscular dysplasia changes found in the evolution of SAM. Varying degrees of mesangial cell hyperplasia accompanied SAM in swine, dog and scattered human cases of SAM. Segmental sclerosis of glomerular loops accompanied the mesangial cell hyperplasia in a few cases of SAM. The hyperplasia was not extensive so that its role in regulating blood flow and urine volume through glomerular capillaries was probably inconsequential. It represented a collateral lesion created by SAM’s norepinephrine driven pathogenesis. Conclusion: These findings provide indirect evidence that SAM additionally may be initiated by conditions causing the adrenal medulla to release supra physiologic levels of circulating norepinephrine. Supra physiologic release of norepinephrine from the peripheral sympathetic nerves also can cause mesangial hyperplasia that can be accompanied with segmental glomerular loop sclerosis-making it another precursor lesion of focal segmental glomerulosclerosis.

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis

Background/Aims: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB–induced mesangial cell proliferation in vitro. Methods: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. Results: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB– stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB–stimulated cells. Conclusion: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB–stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.

Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury.

The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV) and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs), serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC) activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6 × 106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+ T lymphocytes, due to an increase in the percentage of CD8+ T lymphocytes and a decrease in the percentage of CD4+ T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

Growth hormone (GH)-transgenic insulin-like growth factor 1 (IGF1)-deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth.

Growth hormone (GH)‐transgenic mice with permanently elevated systemic levels of GH and insulin‐like growth factor 1 (IGF1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF1‐dependent and ‐independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF1‐deficient (I −/−) and of IGF1‐deficient GH‐transgenic mice (I −/− /G), as well as of GH‐transgenic (G) and nontransgenic wild‐type control mice (I +/+) were examined by quantitative stereological and functional analyses. Both G and I −/− /G mice developed glomerular hypertrophy, hyperplasia of glomerular mesangial and endothelial cells, podocyte hypertrophy and foot process effacement, albuminuria, and glomerulosclerosis. However, I −/− /G mice exhibited less severe glomerular alterations, as compared to G mice. Compared to I +/+ mice, G mice exhibited renal hypertrophy with a significant increase in the number without a change in the size of proximal tubular epithelial (PTE) cells. In contrast, I −/− /G mice did not display significant PTE cell hyperplasia, as compared to I −/− mice. These findings indicate that GH excess stimulates glomerular growth and induces lesions progressing to glomerulosclerosis in the absence of IGF1. In contrast, IGF1 represents an important mediator of GH‐dependent proximal tubular growth in GH‐transgenic mice.

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney.