Mesangial Proliferative Nephritis Research Articles

Association of podocyte injury with clinical features and prognosis in patients with mesangial proliferative lupus nephritis.

The aim of this study is to explore the association of podocyte injury with clinical features and outcomes in mesangial proliferative (Class II) lupus nephritis (LN). We conducted a retrospective and clinicopathologic analysis with 576 LN patients with renal biopsy and screened 58 patients with Class II LN. Then, the 58 cases were divided into 4 groups based on the degree of podocyte damage and immune complex (IC) deposits on light microscope (histological and immunofluorescence) and electron microscope: Podocyte Injury Group, IC deposits Group, Podocyte Injury and IC Group, and Less-lesion Group. Clinical and pathologic information was collected from the patients' medical records at the time of the kidney biopsy and at follow-up. The data of demography, clinical parameters, therapy, remission, and relapse rates were analyzed and compared across groups. A significant difference was observed in the ages of patients among four Class II LN groups. The onset age of patients with FPE ≥ 50% was significant later. The frequency of thrombocytopenia was statistically different among the four groups and the patients with FPE ≥ 50% had lower frequency of thrombocytopenia. Patients with FPE ≥ 50% had lower serum albumin, eGFR, and elevated proteinuria and serum lipids. In this study, most patients received glucocorticoids in combination with immunosuppressants. Among the 4 groups, the use of ACEI/ARBs was highest in the podocyte injury group. There was a statistical difference in the renal relapse rates among the 4 Class II LN groups. Moreover, the recurrence rate was higher in the FPE ≥ 50% group. Our data identified Class II LN patients with podocyte injury (FPE ≥ 50%) present prominent renal damage and higher rate of renal relapse, suggesting more aggressive treatment and close follow-up for these patients.

The pathological and outcome characteristics of renal lesions in Crohn’s disease

BackgroundThe inflammatory bowel disease, containing Crohn’s disease and ulcerative colitis, was rare in the population, especially in the complication of kidney disease. A few studies had found proteinuria played a potential indicator of inflammatory bowel disease occurrence and activity. This study aimed to better define the histopathologic spectrum and study the outcome of renal disease in Crohn’s disease.MethodsA retrospective study of 3557 Crohn's disease from January 1st, 2016 to July 1st, 2021 in the Sixth Affiliated Hospital of Sun Yat-sen University identified 20 (0.56% [20/3557]) patients who underwent kidney biopsy. All biopsy specimens were examined by standard procedures containing light microscopy, immunofluorescence, and electron microscopy.ResultsTwenty cases were shown in this review study. Subnephrotic proteinuria (30% [6 of 20]), persistent hematuria and proteinuria (25% [5 of 20]), and isolated hematuria with acanthocytes (25% [5 of 20]) were the main indications for kidney biopsy. The most common diagnosis was IgA nephropathy (70% [14/20]), followed by minimal change disease (10% [2/20]), acute interstitial nephritis (5% [1/20]), granulomatous interstitial nephritis (5% [1/20]), non-IgA mesangial proliferative nephritis (5% [1/20]) and thin basement membrane nephropathy (5% [1/20]). The Lee classification of IgA nephropathy was mostly II or III level. Glomerular mesangial hyperplasia was the most common pathologic manifestation according to the MEST-C Sore. After twelve-month treatment, the majority of patients turned to complete remission of renal disease by measuring proteinuria, while 3 patients still stayed in the relapse stage and 6 patients turned to partial remission by measuring hematuria.ConclusionsIgA nephropathy is the most common kidney biopsy diagnosis in Crohn's disease. Renal damage in Crohn's disease mainly involves the glomerulus, especially the mesangial matrix. After the treatment, proteinuria might be in remission, but hematuria remains.

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients.

This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological transformation in Chinese patients. 104 SLE patients with biopsy-proven LN class II were included and divided into proteinuria group (proteinuria ≥ 0.4g/24h, with or without microscopic hematuria) and hematuria group (microscopic hematuria with proteinuria < 0.4g/24h).Patients were treated with glucocorticoid alone (GC monotherapy) or GC in combination with other immunosuppressant (combination therapy). The rates of remission, relapse, histological transformation, end-stage renal disease (ESRD), adverse events, and risk factors related to the outcomes were analyzed. During the median follow-up of 77.5 (IQR 58-116.5) months, all the 104 patients achieved remission. Relapse occurred in 69 cases (66.3%), of which 37 were of renal relapse (35.6%). Histological transformation was found in 14 of the 16 (87.5%) cases who received repeated renal biopsy after renal relapse. At the end of follow-up, 3 (2.9%) patients developed ESRD. There were no significant differences in the rates of relapse, histological transformation, adverse events and in the time from remission to relapse between the proteinuria group and the hematuria group. In contrast, the cumulative relapse rate in the GC monotherapy group was much higher than that in the combination group (P < 0.01). Adverse events occurred in 55 (57.3%) patients during follow-up. Patients with LN class II have high rates of relapse and renal histological transformation and need optimal maintenance therapy. • The rates of relapse and histological transformation are high in patients with LN class II. • Patients with LN class II are suggested to receive combination therapy and consider repeat renal biopsy after renal relapse.

Krϋppel-like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation.

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previously determined that Krϋppel‐like factor 15 (KLF15), a kidney‐enriched zinc‐finger transcription factor, was required for inhibition of MC proliferation. In the present study, we investigated the direct target gene and the underlying mechanism by which KLF15 regulated mesangial proliferation. First, we screened small ubiquitin‐related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated this finding with ChIP‐PCR and luciferase assays. Furthermore, we demonstrated that overexpressing KLF15 or SUMO1 enhanced the stability of P53, which blocked the cell cycle of human renal MCs (HRMCs) and therefore abolished cell proliferation. Conversely, knockdown of SUMO1 in HRMCs, even those overexpressed with KLF15, could not inhibit HRMC proliferation rates and increase SUMOylation of P53. Finally, the results showed that the levels of SUMOylated P53 in the kidney cortices of anti‐Thy 1 model rats were decreased during proliferation periods. These findings reveal the critical mechanism by which KLF15 targets SUMO1 to mediate the proliferation of MCs.

Clinical and morphologic spectrum of renal involvement in idiopathic hypereosinophilic syndrome.

To explore the clinical and pathological features of renal lesions in patients with kidney involvement in idiopathic hypereosinophilic syndrome (IHES). The demographic, clinical, and pathological characteristics and the treatment and follow-up data were analyzed. We identified 18 patients with IHES and renal involvement. Eleven patients presented with nephrotic syndrome, and 6 patients had impaired renal function. 15 patients underwent renal biopsy, and the pathological findings included the following: membranoproliferative glomerulonephritis in 3 patients; minimal-change disease in 3; mesangial proliferative nephritis in two; IgA nephropathy in 2; membranous nephropathy in two; chronic interstitial nephritis in two; focal segmental sclerosis in one; and eosinophil infiltration into the renal interstitium in 11 and into the glomerulus in 3. After treatment with glucocorticoids, the eosinophil count decreased. 15 patients werefollowed up, and 14 showed a decrease in urinary protein or renal function recovery. When glucocorticoids were discontinued, eosinophil increased (8 cases), urine protein increased (1 case), and 1 patient progressed to end-stage renal disease. Nephrotic syndrome with or without renal insufficiency is the main clinical manifestation. A wide spectrum of renal lesions can be observed in patients with IHES. Eosinophil infiltration into the renal interstitium was common in these patients. Most patients have a good prognosis after glucocorticoid therapy.

Annals for Educators - 19 February 2019.

Annals for Educators - 19 February 2019.

The Src homology and collagen A (ShcA) adaptor protein may participate in the pathogenesis of membranous lupus nephritis.

The Src homology and collagen A (ShcA) adaptor protein that binds to tyrosine kinase receptors. ShcA plays a role in insulin signaling, stress resistance and energy metabolism. The 66-kDa Src homology 2 domain-containing protein (p66shc) belongs to the ShcA family and has been associated with reactive oxygen species (ROS); increased ROS is involved in the pathology of lupus nephritis (LN). However, whether ShcA can act as a biomarker for oxidative injury in LN is unknown. This study is aimed to investigate the ShcA expression in kidney tissues from patients presenting with LN and the association between ShcA expression and clinical parameters. Renal biopsy tissues were obtained from 62 LN, 20 primary membranous nephropathy (MN) and 10 other secondary MN patients. ShcA was measured by immunofluorescence. The expression of ShcA in the membranous lupus nephritis (class V) group showed a higher trend but there were no significant differences compared with pure mesangial disease (class II) and proliferative (Class III/IV) lupus nephritis. ShcA deposits were negative in primary and other secondary MN. ShcA might act as a new biomarker and a diagnostic tool to identify membranous lupus nephritis with other MN.

Pregnancy-triggered triple autoimmunity (Hashimoto’s thyroiditis, antiphospholipid syndrome and systemic lupus erythematosus)

Introduction: We describe a case of 22 year old female with her first pregnancy triggered Hashimoto’s thyroiditis (HT), Antiphospholipid Syndrome (APS) and Systemic Lupus Erythematosus (SLE). Case Report: A 22 year old female was diagnosed with HT on levothyroxine during the early first trimester. During 21 weeks of gestation patient has intrauterine fetal demise and underwent medical abortion. SLE work up including antinuclear antibody and anti-double stranded DNA were positive. She underwent kidney biopsy, which revealed membranous and mesangial proliferative lupus nephritis. Diagnosis of SLE and APS was made. Treatment with anticoagulation therapy was started. SLE therapy was initiated with prednisone, mycophenolate mofetil and hydroxychloroquine with complete resolution of symptoms.We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. Discussion: APS is a prothrombotic disorder with various manifestations, most commonly venous and arterial thromboembolism and recurrent pregnancy loss. Pregnancy may trigger an underlying APS, which may well be the causative for the miscarriage. New onset SLE during pregnancy is rare. However, in our case, the anemia, thrombocytopenia, and proteinuria led us to the correct diagnosis of SLE. HT is associated with higher rates of infertility and early miscarriages, due to the associated hormonal changes and instability. However, the association of APS and HT is not well recognized in pregnant women. Conclusion: We present here a challenging case of new-onset triple autoimmune disorders trigged by pregnancy. Clinicians should be aware of this association and initiate early autoimmune work up for SLE and APS in patients with new onset of HT during pregnancy. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Pregnancy triggered Hashimoto’s thyroiditis, Antiphospholipid Syndrome and Systemic Lupus Erythematosus

Pregnancy-triggered triple autoimmunity (Hashimoto’s thyroiditis, antiphospholipid syndrome and systemic lupus erythematosus)

Introduction: We describe a case of 22 year old female with her first pregnancy triggered Hashimoto’s thyroiditis (HT), Antiphospholipid Syndrome (APS) and Systemic Lupus Erythematosus (SLE). Case Report: A 22 year old female was diagnosed with HT on levothyroxine during the early first trimester. During 21 weeks of gestation patient has intrauterine fetal demise and underwent medical abortion. SLE work up including antinuclear antibody and anti-double stranded DNA were positive. She underwent kidney biopsy, which revealed membranous and mesangial proliferative lupus nephritis. Diagnosis of SLE and APS was made. Treatment with anticoagulation therapy was started. SLE therapy was initiated with prednisone, mycophenolate mofetil and hydroxychloroquine with complete resolution of symptoms. We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. Discussion: APS is a prothrombotic disorder with various manifestations, most commonly venous and arterial thromboembolism and recurrent pregnancy loss. Pregnancy may trigger an underlying APS, which may well be the causative for the miscarriage. New onset SLE during pregnancy is rare. However, in our case, the anemia, thrombocytopenia, and proteinuria led us to the correct diagnosis of SLE. HT is associated with higher rates of infertility and early miscarriages, due to the associated hormonal changes and instability. However, the association of APS and HT is not well recognized in pregnant women. Conclusion: We present here a challenging case of new-onset triple autoimmune disorders trigged by pregnancy. Clinicians should be aware of this association and initiate early autoimmune work up for SLE and APS in patients with new onset of HT during pregnancy. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Pregnancy triggered Hashimoto’s thyroiditis, Antiphospholipid Syndrome and Systemic Lupus Erythematosus

Predictive Factors and Long Term Outcome in Lupus Nephritis in Libya

Lupus Nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The main purpose of this study is evaluation lupus nephritis, outcome of lupus nephritis, and studies predictive factors in lupus nephritis are improved outcome. Patient and methods: Follow up study patients diagnosed as Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR), from the registration file of Rheumatology clinic, These patients were studied clinically for the presence of lupus nephritis, laboratory test CBP, ESR, RFT, Urine sedimentation, USS Abdomen, Doppler renal and use immunology test ANA positively was more than 1:160, anti-DNA Serum compliment levels (C3, C4), anti-ENA. Result: Clinical presentation of lupus nephritis was asymptomatic lupus nephritis is (6.6%), Nephritis lupus nephritis (24 h urine collection<3 g/d) is (36.8%), Nephrotic disease (24 h urine collection ≥ 3 g/d) is (28.9%) and acute renal failure is (27.6%), Albumin urine collection g/d range from 0.6-6 g/24 h, M=2.1 ± 1.1, blood urea ranged from 18-200 mg/dl, M=90.9 ± 47.6, serum creatinine was 0.5-6.7 mg/dl, M=2.6 ± 1.8, Hypertension patients of lupus nephritis was (89.5%). Positive ANA was (93.4%), positive Ds DNA was (94.7%), and low complement C3, C4 was (94.7%) and positive anti cardiolipin antibody AGL was (23.7%) recurrent attack lupus nephritis was (14.5%). The renal biopsy was done found diffuse proliferative lupus nephritis was (45.5%), Focal proliferative lupus nephritis was (20.8%) and mesangial proliferative lupus nephritis was (16.9%). management of lupus nephritis and choice of therapy according guideline European League against Rheumatism (EULAR), patients were received azathioprine (13.2%), IV injection Cyclophosphamide therapy was (21.1%), mycophenolate mofetil was (55.3%) and injection rituximab was (10.5%). Outcome lupus nephritis was complete response (64.5%), Partial response was (13.2%), resistance lupus nephritis was (22.1%), end stage renal failure on hemodialysis was (7.9%), conservative chronic renal failure was (14.5%) and mortality of lupus nephritis was (13.2%) Conclusion: Most common type diffuse proliferative lupus nephritis followed Focal proliferative lupus nephritis then mesangial proliferative lupus nephritis, induction therapy with mycophenolate mofetil or cyclophosphamide or rituximab in inducing complete remission of lupus nephritis is 64%. Even with standard therapy the end stage renal failure was (14.5%) and mortality of lupus nephritis was (13.2%) in this study. The impact of several factors like sex, age, race, duration of lupus nephritis, serum urea, serum creatinine and renal biopsy have statistical significance correlation and predictive effect on outcome lupus nephritis.

AJKD Atlas of Renal Pathology: Minimal Mesangial and Mesangial Proliferative Lupus Nephritis (ISN/RPS Class I and II)

AJKD Atlas of Renal Pathology: Minimal Mesangial and Mesangial Proliferative Lupus Nephritis (ISN/RPS Class I and II)

Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion.

Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α-smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.

Screening for potential serum biomarkers in rat mesangial proliferative nephritis.

Mesangial proliferative nephritis (MesPGN) is a common kidney disease worldwide. The main feature of the disease is mesangial cell proliferation-induced injury to kidney function. In this study, we explored serum biomarkers for kidney function injury in anti-Thy1 nephritis. We found that mesangial proliferation were increased on days 5 and 7, and recovered by day 14 in anti-Thy1 nephritis. 24-h urine protein, the ratio of urine protein to urine creatine, serum creatine, and blood urea nitrogen, were increased at days 5 and 7 in the model. We found that TXN, BET1, PrRP, VGF, and NPS differed strongly from controls on days 5 and, associated with kidney injury when detected by SELDI-TOF MS. Moreover, we applied LC-MS to detect differential protein expression and found A2M, C3, ITIH4, ITIH3, VDBP, AFM, and SERPINF2 to be upregulated, and ES1, HPX, SERPINC1, SERPINA1F, SERPINA4, SERPINA3K, SPI, TF, VNN3, SERPINF1, and PON1 to be downregulated, on days 5 and 7, associated with kidney injury. The levels of VNN3 and VDBP were validated by Western blotting. Overall, this study explored a group of candidate biomarkers of mesangial proliferation inducing kidney injury, to provide the basis of an assessment model for MesPGN in the future.

Afadin is localized at cell–cell contact sites in mesangial cells and regulates migratory polarity

In kidney glomeruli, mesangial cells provide structural support to counteract for expansile forces caused by pressure gradients and to regulate the blood flow. Glomerular injury results in proliferation and aberrant migration of mesangial cells, which is the pathological characteristic of mesangial proliferative glomerulonephritis. To date, molecular changes that occur in mesangial cells during glomerular injury and their association with the pathogenesis of glomerulonephritis remain largely unclear. During the search for proteins regulating the morphology of mesangial cells, we found that afadin, a multi-domain F-actin-binding protein, and β-catenin are expressed in cell–cell contact sites of cultured mesangial cells and mesangial cells in vivo. Afadin forms a protein complex with β-catenin in glomeruli and in cultured mesangial cells. Protein expression of afadin at mesangial intercellular junctions was dramatically decreased in mesangial proliferative nephritis in rats and in patients with glomerulonephritis. RNA interference-mediated depletion of afadin in cultured mesangial cells did not affect proliferation rate but resulted in delayed directional cell migration. Furthermore, reorientation of the Golgi complex at the leading edges of migrating cells in wound-healing assay was disturbed in afadin-depleted cells, suggesting the role of aberrant migratory polarity in the pathogenesis of proliferative glomerulonephritis. These data shed light on glomerulonephritis-associated changes in cell–cell adhesion between mesangial cells, which might be related to migratory polarity.

Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis.

BackgroundMesangial cell (MC) proliferation and apoptosis are the main pathological changes observed in mesangial proliferative nephritis. In this study, we explored the role of cyclins and p53 in modulating MC proliferation and apoptosis in a mouse model of Habu nephritis.MethodsThe Habu nephritis group was prepared by injection of Habu toxin. Mesangiolysis and mesangial expansion were determined by periodic acid-Schiff (PAS) reagent staining. Immunohistochemical analysis of PCNA and KI67, and TUNEL staining were used to detect cell proliferation and apoptosis, respectively. Expression levels of cyclins and p53 were examined by Western blotting.ResultsPAS staining showed that mesangial dissolution appeared on days 1 and 3, and mesangial proliferation with extracellular matrix accumulation was apparent by days 7 and 14. Both PCNA and KI67 immunohistochemical analysis showed that MC proliferation began on day 3, peaked on day 3 and 7, and recovered by day 14. TUNEL staining results showed that MC apoptosis began to increase on day 1, continued to rise on day 7, and peaked on day 14. Western blot analysis showed that cyclin D1 was upregulated on day 1, cyclins A2 and E were upregulated on days 3 and 7, and p53 was upregulated on days 3, 7 and 14. There was no change in the expression levels of Bax or p21.ConclusionWe explored the tendency for MC proliferation and apoptosis during the process of Habu nephritis and found that cyclins and p53 may modulate the disease pathology. This will help us determine the molecular pathogenesis of MC proliferation and provide new targets for disease intervention.

FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell.

The apoptosis of mesangial cells (MCs) plays a critical role in the pathological progress of MesPGN. Septin2, a filamentous GTPase, is implicated in the apoptotic progress of MCs in the rat MesPGN model. However, the molecular mechanism of SEPT2 in MCs apoptosis is not clear. Here, we present the FHL2-driven molecular network as the main mechanism of SEPT2-mediated rat primary MCs apoptosis. First, we proved that the expression of FHL2 and Septin2 were closely related with MCs apoptosis in anti-Thy1 nephritis model. Then, it was found that FHL2 was a new interaction protein of Septin2 and Septin2 knockdown could induce MC apoptosis by FHL2-mediatied signal pathways including p-ERK1 and p-AKT. We applied label-Free quantitative proteomics to identify the mechanism of Septin2/FHL2-regulated apoptosis. Bioinformatics analysis revealed that FHL2-driven molecular network composed of biological functions including glycolysis, oxidative stress, ribonucleotide metabolism, actin cytoskeleton regulation, and signaling pathway, was the main mechanism of SETP2-mediated apoptosis. Furthermore, we showed that the effect of Septin2 knockdown on MC apoptosis could be alleviated by the overexpression of FHL2. Overall, this study illustrated the FHL2-driven molecular network controlling SEPT2-mediated apoptosis in MCs and their potential roles in mesangial proliferative nephritis.

Epithelial protein lost in neoplasm modulates platelet-derived growth factor–mediated adhesion and motility of mesangial cells

Mesangial cell migration, regulated by several growth factors, is crucial after glomerulopathy and during glomerular development. Directional migration requires the establishment of a polarized cytoskeletal arrangement, a process regulated by coordinated actin dynamics and focal adhesion turnover at the peripheral ruffles in migrating cells. Here we found high expression of the actin cross-linking protein EPLIN (epithelial protein lost in neoplasm) in mesangial cells. EPLIN was localized in mesangial angles, which consist of actin-containing microfilaments extending underneath the capillary endothelium, where they attach to the glomerular basement membrane. In cultured mesangial cells, EPLIN was localized in peripheral actin bundles at focal adhesions and formed a protein complex with paxillin. The MEK-ERK (extracellular signal-regulated kinase) cascade regulated EPLIN-paxillin interaction and induced translocalization of EPLIN from focal adhesion sites to peripheral ruffles. Knockdown of EPLIN in mesangial cells enhanced platelet-derived growth factor-induced focal adhesion disassembly and cell migration. Furthermore, EPLIN expression was decreased in mesangial proliferative nephritis in rodents and humans in vivo. These results shed light on the coordinated actin remodeling in mesangial cells during restorative remodeling. Thus, changes in expression and localization of cytoskeletal regulators underlie phenotypic changes in mesangial cells in glomerulonephritis.

FRI0403 Mesangial Proliferative Lupus Nephritis (ISN/RPS CLASS II): Clinical and Prognosis in A Cohort of 45 Patients

BackgroundMesangial proliferative lupus nephritis (MPLN) or class II has traditionally been considered a mild form of nephritis, with good response to corticosteroid treatment. However, recently some studies have been published...

MiR-34a regulates mesangial cell proliferation via the PDGFR-β/Ras-MAPK signaling pathway

The main pathological characteristic of glomerulonephritis is diffuse mesangial cell proliferation. MiR-34a is associated with the proliferation of various organs and cancer cells. However, the role of miR-34a in renal proliferation diseases is not clear. Therefore, this study aimed to elucidate the mechanism of miR-34a in the regulation of renal mesangial cell proliferation. The miR-34a expression level at different time points in an anti-Thy1 mesangial proliferative nephritis rat model was determined by qRT-PCR. The cell proliferation rate and cell cycle changes were measured in the in vitro cultured rat mesangial cells (RMCs). Our results suggested that miR-34a expression was negatively correlated with the degree of cell proliferation in the anti-Thy1 nephritis model. MiR-34a could extend the G0/G1 phase and block cell proliferation in RMCs. Dual-luciferase assay results showed that there were binding sites of miR-34a at 3′-UTR of platelet-derived growth factor receptor-β (PDGFR-β). MiR-34a can inhibit PDGFR-β protein expression at a post-transcriptional level, suppress Ras/MAPK signaling pathways, and down-regulate expression of cell cycle proteins at the G0/G1 phase, such as cyclin D1, CDK4/CDK6. In addition, miR-34a may also inhibit RMC proliferation by directly targeting cyclin E and CDK2. MiR-34a inhibits exogenous stimuli-induced proliferation of mesangial cells. Expression levels of phospho-PDGFR-β and phospho-MEK1 (an important downstream molecule in PDGFR-β-induced signaling pathway) were significantly increased in the anti-Thy-1 nephritis rat model. These results suggest that miR-34a may regulate RMC proliferation by directly inhibiting expressions of PDGFR-β, MEK1, and cell cycle proteins, cyclin E and CDK2.

Nephrotic syndrome due to mesangial proliferative lupus nephritis (ISN /RPSclass II):Acase report

Galle Medical Journal, Vol 18: No. 1, March 2013, Page 54-56 DOI: http://dx.doi.org/10.4038/gmj.v18i1.5509