Roles of the podocyte in glomerular function

Pavenstädt, Hermann

doi:10.1152/ajprenal.2000.278.2.f173

Cited by 117 publications

(103 citation statements)

References 47 publications

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“…Due to species differences, proteinuria is not observed in adult mice given the same dose of PAN (0.1 mg/g) [12]. In addition, intraperitoneal injection could lead to tolerance, which prevents the reproduction of MCD model in mice [13]. Wang et al [14] showed that a single epidermal injection of PAN (0.5 mg/g) in mice can generate excess urine protein, thus reproducing the classic rat disease model in mice.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes

Chen

Wan

Gao

et al. 2017

CIM

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Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes Abstract Purpose: The purpose of this study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) on podocytes of puromycin amino nuclear glucoside (PAN) -induced nephrosis in mice.Methods: Mice were randomly divided into Control, PAN and BMSC groups. Mice were injected with PAN (0.5 mg/g weight) via the tail vein. The 24-h urinary protein was obtained after modelling, and urinary protein excretion was determined. The blood and kidney specimens were isolated after the tenth day of modelling. Blood samples were collected for measuring serum creatinine (SCr) and blood urea nitrogen (BUN). A sample of kidney was taken for observing pathological changes through hematoxylin-eosin staining and electron microscopy, and the rest of the kidney was used for detecting the protein and mRNA expression of nephrin, CD2AP, synaptopodin, TRPC6 by real-time quantitative PCR, Western-blot and immunohistochemistry.Results: After PAN injection, podocyte foot process fusion was detected by electron microscopy, and the 24 h urinary protein excretion increased compared with control mice on days 3, 7 and 10 post-PAN injection (P<0.05). Serum albumin decreased compared with control mice after day 10 (P<0.05). The phenomenon of foot process fusion was ameliorated after administration of BMSC, and 24 h urinary protein decreased (P<0.05), while serum albumin increased (P<0.05). Nephrin, CD2AP and synaptopodin in the glomerular slit diaphragm were up-regulated compared to PAN nephropathy model mice (P<0.05) while TRPC6 was down-regulated (P<0.05).Conclusions: Administration of BMSC reduced foot process fusion and urine protein excretion, and protected against podocyte damage caused by PAN.

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Section: Discussionmentioning

confidence: 99%

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes

Chen

Wan

Gao

et al. 2017

CIM

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“…To test the association with glomerular function, the glomerular regulation of the podocyte gene set discovered by nanodissection was compared between 39 controls and 17 patients with FSGS, a renal disease caused by severe podocyte damage (Kriz et al 1994;Pavenstädt 2000) and the leading cause of glomerular failure in children. Using significance analysis of microarrays (SAM) (Tusher et al 2001), 60 of the 136 genes identified by nanodissection were significantly repressed in glomeruli from FSGS patients versus controls (q-value < 0.05).…”

Section: Disease-specific Regulation Of the Nanodissection Gene Setsmentioning

confidence: 99%

Defining cell-type specificity at the transcriptional level in human disease

et al. 2013

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Cell-lineage–specific transcripts are essential for differentiated tissue function, implicated in hereditary organ failure, and mediate acquired chronic diseases. However, experimental identification of cell-lineage–specific genes in a genome-scale manner is infeasible for most solid human tissues. We developed the first genome-scale method to identify genes with cell-lineage–specific expression, even in lineages not separable by experimental microdissection. Our machine-learning–based approach leverages high-throughput data from tissue homogenates in a novel iterative statistical framework. We applied this method to chronic kidney disease and identified transcripts specific to podocytes, key cells in the glomerular filter responsible for hereditary and most acquired glomerular kidney disease. In a systematic evaluation of our predictions by immunohistochemistry, our in silico approach was significantly more accurate (65% accuracy in human) than predictions based on direct measurement of in vivo fluorescence-tagged murine podocytes (23%). Our method identified genes implicated as causal in hereditary glomerular disease and involved in molecular pathways of acquired and chronic renal diseases. Furthermore, based on expression analysis of human kidney disease biopsies, we demonstrated that expression of the podocyte genes identified by our approach is significantly related to the degree of renal impairment in patients. Our approach is broadly applicable to define lineage specificity in both cell physiology and human disease contexts. We provide a user-friendly website that enables researchers to apply this method to any cell-lineage or tissue of interest. Identified cell-lineage–specific transcripts are expected to play essential tissue-specific roles in organogenesis and disease and can provide starting points for the development of organ-specific diagnostics and therapies.

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“…32 Thus, we next investigated whether the observed Ang II effects could be related to activation of AT 1 receptors, which are expressed in the murine podocyte line. 33 Pretreatment of podocytes with the specific AT 1 receptor antagonist L-158,809 prevented both the redistribution of ZO-1 ( Figure 5, c versus b; Table 1) and the increase in albumin permeability by Ang II (Figure 5d).…”

Section: Role Of At 1 Receptors In Zo-1 Redistribution and Podocyte Dmentioning

confidence: 99%

Permselective Dysfunction of Podocyte-Podocyte Contact upon Angiotensin II Unravels the Molecular Target for Renoprotective Intervention

Macconi

Abbate

Morigi

et al. 2006

The American Journal of Pathology

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Ameliorating the function of the glomerular barrier to circulating proteins by blocking angiotensin II (Ang II) translates into less risk of progression toward endstage renal failure in diabetic and nondiabetic nephropathies. However, the mechanisms underlying this barrier protection are not clear. Specialized contacts between adjacent podocytes are major candidate targets, and the actin cytoskeleton is emerging as a regulatory element. Here, we present data demonstrating that Ang II induced reorganization of F-actin fibers and redistribution of zonula occludens-1 (ZO-1) that is physically associated with actin in murine podocytes. These effects were paralleled by increased albumin permeability across podocyte monolayers. The F-actin stabilizer jasplakinolide prevented both ZO-1 redistribution and albumin leakage, suggesting that actin cytoskeleton rearrangement is instrumental to podocyte permselective dysfunction induced by Ang II. Changes in both F-actin and ZO-1 patterns were confirmed in glomeruli of rat isolated perfused kidneys on short infusion of Ang II, leading to increased protein excretion. Podocyte dysfunction was mediated by Ang II type 1 receptor and was partly dependent on Src kinase-phospholipase C activation. These data demonstrate that strategies aimed at stabilizing podocyte-podocyte contacts and targeting the relevant intracellular signal transduction are crucial to renoprotection.

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Roles of the podocyte in glomerular function

Cited by 117 publications

References 47 publications

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes

Defining cell-type specificity at the transcriptional level in human disease

Permselective Dysfunction of Podocyte-Podocyte Contact upon Angiotensin II Unravels the Molecular Target for Renoprotective Intervention

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