Infiltration Of Kidney Research Articles

Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage

A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial–mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0–3, 6–9 or 10–13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.

Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n=60) and Coot (n=50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n=5) and high concentrations (Mallards n=18 and Coots n=17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions.

A Competitive Infection Model of Hematogenously Disseminated Candidiasis in Mice Redefines the Role of Candida albicans IRS4 in Pathogenesis

Candida albicans IRS4 encodes a protein that regulates phosphatidylinositol-(4,5)-bisphosphate, which was shown to contribute to hematogenously disseminated candidiasis (DC) after several days in the standard mouse model. Our objective was to more accurately define the temporal contributions of IRS4 to pathogenesis. During competition assays in vitro, an irs4-null (Δirs4) mutant exhibited wild-type fitness. In DC experiments, mice were infected intravenously with the Δirs4 mutant, strain CAI-12 (1 × 10(5) CFU), or a mixture of the strains (0.5 × 10(5) CFU each). In single-strain infections, quantitative PCR revealed reduced Δirs4 mutant burdens within kidneys at days 1, 4, and 7 but not 6 h. In competitive infections, the Δirs4 mutant was outcompeted by CAI-12 in each mouse at ≥6 h (competitive indices, P ≤ 0.0001). At 4 and 7 days, the Δirs4 mutant burdens during competitive infections were significantly lower than those during single-strain infections (P = 0.01 and P < 0.001, respectively), suggesting increased susceptibility to inflammatory responses. Phagocytic infiltration of kidneys in response to CAI-12 or competitive infections was significantly greater than that in response to Δirs4 mutant infection at days 1 and 4 (P < 0.001), and the Δirs4 mutant was more susceptible to phagocytosis and killing by human polymorphonuclear cells (P = 0.01 and P = 0.006, respectively) and mouse macrophages in vitro (P = 0.04 and P = 0.01, respectively). Therefore, IRS4 contributes to tissue invasion at early stages of DC and mediates resistance to phagocytosis as DC progresses. Microarray analysis revealed remarkably similar gene expression by the Δirs4 mutant and reference strain CAI-12 within blood, suggesting that IRS4 is not significantly involved in the hematogenous stage of disease. A competitive DC model detects attenuated virulence that is not evident with the standard model.

Involvement of N-type Ca2+channels in the fibrotic process of the kidney in rats

N-type Ca(2+) channels are densely distributed in sympathetic nerves that innervate renal tubules. However, the role of N-type Ca(2+) channels in renal fibrosis remains unknown. To address this issue, we examined the difference between the effects of amlodipine (an L-type Ca(2+) channel blocker) and cilnidipine (a dual L/N-type Ca(2+) channel blocker) on fibrotic changes using a rat unilateral ureteral obstruction (UUO) model. The expression of both L-type and N-type Ca(2+) channels was significantly upregulated in UUO kidneys compared with that in contralateral kidneys. There were no significant differences in mean blood pressure among the rats tested. Both amlodipine and cilnidipine significantly attenuated fibrotic changes in UUO kidneys. The antifibrotic effect of cilnidipine was more potent than that of amlodipine. Amlodipine as well as cilnidipine reduced type III collagen deposition, α-smooth muscle actin (α-SMA) expression, and interstitial cell proliferation. In addition, cilnidipine significantly reduced deposition of type I collagen and macrophage infiltration in UUO kidneys. With the use of in vivo bromodeoxyuridine labeling, label-retaining cells (LRCs) were identified as a population of tubular cells that participate in epithelial-mesenchymal transition after UUO. Some LRCs migrated into the interstitium, expressed α-SMA and vimentin, and produced several extracellular matrixes in UUO kidneys. The number of interstitial LRCs was significantly decreased by cilnidipine but not amlodipine. These data suggest that N-type Ca(2+) channels contribute to multiple steps of renal fibrosis, and its blockade may thus be a useful therapeutic approach for prevention of renal fibrosis.

Gastric High-Risk Gist and Retroperitoneal Liposarcoma – A Challenging Combination of Two Mesenchymal Tumor Lesions with Regard to Diagnosis and Treatment

Both gastrointestinal stromal tumors (GIST) and liposarcoma originate from mesenchymal tissue. Their coincidence requires a specific expertise in the diagnostic and therapeutic management. An unusual exemplary case is described representing a 47-year old female patient with a gastric GIST and a monstrous retroperitoneal liposarcoma with infiltration of the left kidney. The gastric tumor lesion was removed with a tangential resection of the gastric wall; the retroperitoneal tumor lesion was resected including the left kidney. Both tumors were resected with no macroscopic tumor residual. The technically difficult surgical intervention did not show any postoperative complication, and the postoperative course was also uneventful. The complete tumor resection is the treatment of choice in mesenchymal tumors (aim: R0). Depending on histologic tumor classification, resection status and tumor sensitivity, a subsequent radiation and/or chemotherapy is necessary, which allowed to achieve a postoperative tumor-free survival of 6 years including a good quality of life.

Bilateral nephromegaly and arthritis: A rare presentation of acute lymphoblastic leukemia

A 2.5 years old boy presented with fever, intermittent small joint arthritis of hands and feet, bilateral nephromegaly with normal hemogram and uric acid level. Bone marrow aspiration revealed pre-B acute lymphoblastic leukemia without leukemic infiltration of kidneys. Leukemia should be suspected in any patient with arthritis and nephromegaly.

Immunosuppression preserves renal autoregulatory function and microvascular P2X1 receptor reactivity in ANG II-hypertensive rats

Autoregulation is critical for protecting the kidney against arterial pressure elevation and is compromised in some forms of hypertension. Evidence indicates that activated lymphocytes contribute importantly to cardiovascular injury in hypertension. We hypothesized that activated lymphocytes contribute to renal vascular dysfunction by impairing autoregulation and P2X(1) receptor signaling in ANG II-infused hypertensive rats. Male Sprague-Dawley rats receiving ANG II infusion were treated with a lymphocyte proliferation inhibitor, mycophenolate mofetil (MMF) for 2 wk. Autoregulation was assessed in vitro and in vivo using the blood-perfused juxtamedullary nephron preparation and anesthetized rats, respectively. ANG II-treated rats exhibited impaired autoregulation. At the single vessel level, pressure-mediated afferent arteriolar vasoconstriction was significantly blunted (P < 0.05 vs. control rats). At the whole kidney level, renal blood flow passively decreased as renal perfusion pressure was reduced. MMF treatment did not alter the ANG II-induced hypertensive state; however, MMF did preserve autoregulation. The autoregulatory profiles in both in vitro or in vivo settings were similar to the responses from control rats despite persistent hypertension. Autoregulatory responses are linked to P2X(1) receptor activation. Accordingly, afferent arteriolar responses to ATP and the P2X(1) receptor agonist β,γ-methylene ATP were assessed. ATP- or β,γ-methylene ATP-induced vasoconstriction was significantly attenuated in ANG II-infused hypertensive rats but was normalized by MMF treatment. Moreover, MMF prevented elevation of plasma transforming growth factor-β1 concentration and lymphocyte and macrophage infiltration in ANG II-infused kidneys. These results suggest that anti-inflammatory treatment with MMF prevents lymphocyte infiltration and preserves autoregulation in ANG II-infused hypertensive rats, likely by normalizing P2X(1) receptor activation.

The cAMP Response Element Binding Protein (CREB) Overexpression Induces Myeloid Transformation in Zebrafish

AbstractAbstract 4727 Introduction.Transcription factors has been widely confirmed to play a central role in acute leukemia, and among them the cyclic-adenosine monophosphate response element-binding protein (CREB) was identified to be involved in triggering acute myeloid leukemia. CREB protein overexpression has been found in the bone marrow of most pediatric patients with acute leukemia, and it has been shown to induce myeloid leukemia progression in vitro and in vivo by driving the upregulation of a series of target genes. CREB is evolutionarily conserved from invertebrates to human, and although the main focus of zebrafish research has traditionally been developmental biology, this model is currently used for cancer research. In fact, tumors induced in ZF have similar morphology and activated signaling pathways of human cancers. Aim.We aimed to develop a ZF harboring CREB overexpression in myeloid precursors, and by monitoring the induced myeloid malignancy, we will characterize CREB signaling and its involvement in the myeloid transformation process. Results.Using a Multisite Gateway System we constructed a vector containing human-CREB gene fused to EGFP, driven by an early myeloid promoter, zPu.1, to induce CREB overexpression specifically in the myeloid lineage of ZF. We injected the EGFP-CREB plasmid into one-cell stage zebrafish embryos, and monitored its expression during early development. Results showed that CREB was expressed in ZF zones typical of myelopoiesis, such as in the intermediate cell mass and anterior lateral mesoderm migrating through the yolk from 12 to 48 hours post-fertilization (hpf), and few cells circulating throughout the embryo from 24 hpf. CREB transcriptional activity on cAMP response elements (CREs) was measured and confirmed by luciferase assay. The co-localization of EGFP-CREB with the CRE-mCherry reporter was seen by fluorescence microscopy analysis. To test CREB target gene expression, embryos injected with CREB or Empty vector were subjected to RNA extraction and RQ-PCR. CREB over-expression was documented (up to 103 fold), and c-myb, stat3, rb, runx1, cyclins A, B, D1 and E2 were found upregulate at 24 and 48 hpf. By RNA whole mount in situ hybridization, we revealed pu.1, mpo, gata1 and fli.1 increased signals, suggesting a general disruption of the main hematopoietic factors.Ten CREB-injected zebrafish have been grown to adulthood and all of them displayed an abnormal/sick phenotype with abdominal enlargement and swelling from 10 to 12 months. Histochemical H&E staining performed on paraffin sections revealed an abdominal tumor and metastatic infiltration in kidney, skin, gills, muscles, adipose tissue. PAS staining identified the myeloid character of the tumor mass and kidney marrow. Wright-Giemsa and ANAE staining showed the predominance of clonal monocytes on appositions of tumor mass and kidney marrow of sick ZF. Tumor mass cell sorting displayed a clonal feature of the tumor with an enrichment of the myeloid-monocitic compartment. RNA extraction from the mass shows CREB overexpression as well as its target genes (c-myb, runx1, cyclin A1, cyclin B1, cyclin B2, cyclin E1), confirming CREB involvement in this tumor formation. Conclusion.We demonstrated that CREB overexpression recapitulates myeloproliferative disorder in ZF, supporting the ZF as a suitable model for studying CREB-induced leukemia. The discovery through which targets CREB would preferentially mediate the myeloid transformation will help to unravel leukemogenesis. ZF model might be useful to test CREB directed drugs. Disclosures:No relevant conflicts of interest to declare.

A case of hepatopulmonary syndrome solved by mycophenolate mofetil (an inhibitor of angiogenesis and nitric oxide production)

The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multisystemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation and autoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multisystemic cases; so far there has been no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment. A teenage boy, diagnosed with ALPS at 4years of age (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13years of age, when he developed insidious hypoxemia (PaO 2 =46.7mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intrapulmonary shunt=45%). He was treated with oxygen (maximum 6L/min), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except for the pulmonary symptoms, therefore, after evaluation in referral centers in England, OLT was proposed. Since he was to undergo major surgery, sirolimus, which has wound-healing problems, was switched to mycophenolate mofetil (MMF). Following this change, we observed a huge improvement in pulmonary symptoms and reduction of oxygen needs. The intrapulmonary shunt decreased from 45% to 0% in less than a year, and it has not changed since (18months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year, lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation. The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in HPS pathogenesis). Therefore, we propose to perform clinical trials with MMF, and/or other angiogenesis and NO inhibitors, on a long-term treatment basis, to confirm their potential as a valid alternative to medical treatment of HPS.

ROLE OF CHEMOKINE RECEPTOR 2 IN RENAL INJURY DURING DOCA-SALT HYPERTENSION

ObjectivesThis study was designed to determine the role of chemokine receptor 2 (CCR2), a receptor of MCP-1, in the development of salt-sensitive hypertension-induced renal damage.MethodsWe induced hypertension by uninephrectomy and...

Sudden onset of renal failure requiring dialysis associated with large B-cell lymphoma of colon

Acute renal failure due to lymphomatous infiltration of the kidneys is an uncommon illness (1). Here, a case of acute renal failure due to lymphomatous infiltration of left kidney in association with renal vein thrombosis and acute tubular necrosis of contralateral kidney due to acute tubular necrosis, resulting in absolute anuria and requiring dialysis is presented.

The TGF-β co-receptor endoglin regulates macrophage infiltration and cytokine production in the irradiated mouse kidney

Background and PurposeWe previously showed that mice with reduced levels of the transforming growth factor-beta (TGF-β) co-receptor endoglin (Eng+/− mice) develop less fibrosis and vascular damage after kidney irradiation than their wild type (Eng+/+ mice) littermates; however, the underlying mechanism was unclear. Results from current studies suggest that this occurs via modulation of the radiation-induced inflammatory response. Materials and methodsKidneys of Eng+/+ and Eng+/− mice were irradiated with 16Gy. Mice were sacrificed at 20weeks after irradiation and gene expression and protein levels were analyzed. ResultsKidney irradiation triggered the infiltration of macrophages in both Eng+/+ and Eng+/− mice, however, levels of macrophage-produced cytokines interleukin 1 beta (Il1b) and interleukin 6 (Il6) were reduced in irradiated Eng+/− compared to Eng+/+ mice. Double immuno-stainings confirmed that IL-6 was produced by macrophages, whereas IL-1β was mainly detected in other cell types. Accordingly, inflammatory cell precursors derived from the bone marrow of Eng+/− mice showed impaired ability to express Il1b and Il6 compared to wild type mice. ConclusionsEndoglin promotes kidney inflammation after irradiation by regulating macrophage infiltration and interleukin production, thereby promoting pathogenic changes after radiation exposure.

Hyperbaric Oxygen Therapy Alleviates Oxidative Stress and Tissue Injury in Renal Ischemia/Reperfusion Injury in Rats

Hyperbaric oxygen (HBO) therapy has been shown to attenuate renal ischemia/reperfusion (I/R) injury in rats, when applied in the early reperfusion period. The aim of this study was to elucidate possible beneficial effects of HBO therapy on renal I/R injury, when applied 24 h after ischemia. Rats were randomized into three groups: (1) control group (n = 20), (2) I/R group (n = 20), and (3) I/R + HBO group (n = 20). Renal I/R injury was created by interrupting renal blood flow for 30 min with a non-traumatic vascular clamp. HBO therapy was administered 24 h after I/R injury and continued for 5 days. At the end of the study, rats were sacrificed under anesthesia, blood was drawn, and right kidneys were harvested for analysis. Renal I/R injury increased serum and tissue malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. HBO therapy attenuated MDA levels by increasing SOD and GPx activities. HBO therapy also prevented neutrophil infiltration and tissue injury in kidneys. Taken together, HBO therapy has been found to be effective in the delayed period of I/R injury.

Abstract 352: Anti-aging Gene Klotho Deficiency Causes Hypertension and Vascular Dysfunction via Upregulation of Mammalian Target of Rapamycin (mTOR)

Klotho is a recently discovered anti-aging gene. Genetic mutation of klotho expedites the aging process and shortens the lifespan while overexpression of klotho slows down the aging process and extends the lifespan by 20%. Interestingly, blood pressure (BP) was elevated significantly and vasodilatory responses to acetylcholine and sodium nitroprusside were impaired in klotho heterozygeous (+/-) mice, suggesting that klotho deficiency causes hypertension and vascular dysfunction. It is noted that klotho deficiency is associated with upregulation of mTOR expression and NADPH oxidase activity and downregulation of Mn-SOD expression in aortas and kidneys. Inhibition of mTOR by rapamycin abolished the upregulation of NADPH oxidase activity and O 2 - production and the downregulation of Mn-SOD expression and decreased BP to the control levels. Inhibition of mTOR also abolished vascular endothelial dysfunction and macrophage infiltration in kidneys in klotho (+/-) mice. The upregulation of NADPH oxidase activity and downregulation of Mn-SOD may be involved in klotho deficiency-induced hypertension which can be decreased significantly by apocynin (NADPH oxidase inhibitor) or Tempol (O 2 - scavenger). These results demonstrate, for the first time, that klotho is essential in the maintenance of normal blood pressure. Klotho deficiency-induced hypertension and vascular dysfunction are mediated by upregulation of mTOR. This study also reveals a previously unidentified role of mTOR in the regulation of NADPH oxidase and MnSOD. (Supported by HL105302 and HL102074).

Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus

Chronic nasal and skin colonization with superantigen (SAg)-producing Staphylococcus aureus is well documented in humans. Given that trans-mucosal and trans-cutaneous absorption of SAgs can occur, we determined whether chronic exposure to small amounts of SAg per se could activate autoreactive CD4(+) and CD8(+) T cells and precipitate any autoimmune disease without further external autoantigenic stimulation. Because HLA class II molecules present SAg more efficiently than do mouse MHC class II molecules, HLA-DQ8 transgenic mice were implanted s.c. with mini-osmotic pumps capable of continuously delivering the SAg, staphylococcal enterotoxin B (total of 10 μg/mouse), or PBS over 4 wk. Chronic exposure to staphylococcal enterotoxin B resulted in a multisystem autoimmune inflammatory disease with features similar to systemic lupus erythematosus. The disease was characterized by mononuclear cell infiltration of lungs, liver, and kidneys, accompanied by the production of anti-nuclear Abs and deposition of immune complexes in the renal glomeruli. The inflammatory infiltrates in various organs predominantly consisted of CD4(+) T cells bearing TCR Vβ8. The extent of immunopathology was markedly reduced in mice lacking CD4(+) T cells and CD28, indicating that the disease is CD4(+) T cell mediated and CD28 dependent. The absence of disease in STAT4-deficient, as well as IFN-γ-deficient, HLA-DQ8 mice suggested the pathogenic role of Th1-type cytokines, IL-12 and IFN-γ. In conclusion, our study suggests that chronic exposure to extremely small amounts of bacterial SAg could be an etiological factor for systemic lupus erythematosus.

Renal failure secondary to leukemic infiltration of kidneys in CLL—a case report and review of literature

Renal failure secondary to leukemic infiltration of kidneys in CLL—a case report and review of literature

Analysis of the immune response in infections of the goldfish (Carassius auratus L.) with Mycobacterium marinum

The rapid doubling time and genetic relatedness of the fish pathogen Mycobacterium marinum to Mycobacterium tuberculosis has rendered the former an attractive model for investigating mycobacterial host-pathogen interactions. We employed the M. marinum-goldfish infection model to investigate the in vivo immune responses to this pathogen in the context of a natural host. Histological analysis revealed mycobacterial infiltrates in goldfish kidney and spleen tissues, peaking 28days post infections (dpi). Quantitative gene expression analysis showed significant increases of mRNA levels of pro-inflammatory cytokines (IFNγ, IL-12p40, IL-1β1) and cytokine receptors (IFNGR1-1, TNFR2) at 7dpi. Conversely, the gene expression levels of key anti-inflammatory cytokines TGFβ and IL-10 were elevated at 14dpi. Furthermore, M. marinum infections markedly increased the cytokine-primed oxidative burst responses of isolated kidney phagocytes at 7 but not 56dpi. We believe that the M. marinum-goldfish infection model will be invaluable in furthering the understanding of the mycobacterium host-pathogen interface.

Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart

There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 μM significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor κB activation. In vivo, despite that B06 administration at 0.2 mg·kg−1·d−1 for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy.

Intravenous pyogenic granuloma of the right adrenal gland: report of a case

Pyogenic granuloma (PG) is a tumor-like lesion that typically arises on human skin. Intravenous pyogenic granuloma (IVPG) is the vascular counterpart, mostly observed in the venous structures of the neck and upper extremities. Chronic irritation of the skin, traumatic injury, and hormonal alterations seem to be implicated in the pathogenesis of PG. The incidence of PG, and IVPG, is very low in the reported scientific literature, and this underlines the need for understanding unresolved questions concerning the uncommon presentation, and correct diagnosis before surgical intervention. This report describes a case of IVPG diagnosed in a 55-year-old female that presented for observation of chronic abdominal pain associated with nausea and anorexia. A well-defined mass located in the right adrenal gland was documented by ultrasonography and finally confirmed by contrast enhanced CT of the abdomen. There were no radiological signs of liver, kidney, or vascular infiltration. The 35 × 22 mm adrenal gland lesion, suspected to be an adrenal gland tumor, was resected using a minimally invasive approach. Laparoscopic right adrenalectomy was successfully performed. The histology documented the typical morphological features of IVPG in the context of a normal right adrenal gland. This report describes and discusses the unusual presentation of intraabdominal IVPG located in the adrenal gland region together with a review of the current literature.

Tubular cell dedifferentiation and peritubular inflammation are coupled by the transcription regulator Id1 in renal fibrogenesis

During renal fibrogenesis, tubular epithelial-mesenchymal transition is closely associated with peritubular inflammation; however, it is not clear whether these two processes are connected. We previously identified the inhibitor of differentiation-1 (Id1), a dominant negative antagonist of basic helix-loop-helix transcription factors, as a major trigger of tubular cell dedifferentiation after injury. Id1 was induced selectively in degenerated proximal tubule and collecting duct epithelia after injury and was present in both the cytoplasm and nucleus, suggesting shuttling between these two compartments. Interestingly, the upregulation of Id1 was associated with peritubular inflammation in mouse and human nephropathies. In vitro, Id1 potentiated NF-κB signaling and augmented RANTES expression in kidney epithelial cells, which led to an enhanced recruitment of inflammatory cells. Id1 also induced Snail1 expression and triggered tubular epithelial dedifferentiation. In vivo, genetic ablation of Id1 in mice reduced peritubular inflammation and decreased tubular expression of RANTES following ureteral obstruction. Mice lacking Id1 were also protected against myofibroblast activation and matrix expression, leading to a reduced total collagen deposition in obstructive nephropathy. Thus, these results indicate that Id1 shuttles between nucleus and cytoplasm and promotes peritubular inflammation and tubular epithelial dedifferentiation, suggesting that these two events are intrinsically coupled during renal fibrogenesis.