Podocyte number predicts progression of proteinuria in IgA nephropathy

Xu, Linfeng; Yang, Haichun; Hao, Chuan‐Ming; Lin, Shantan; Gu, Yong; Ma, Ji

doi:10.1038/modpathol.2010.110

Cited by 42 publications

(27 citation statements)

References 54 publications

(57 reference statements)

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“…Moreover, the loss of podocytes into urine contributes to the development of glomerular diseases such as proteinuria [15]. In IgA nephropathy, podocyte injury is involved in the development of proteinuria, and the loss of podocytes predicts the progression of the proteinuria [11]. Thus, we hypothesised that the increased Nestin level in urine samples from PE patients results from the loss of podocytes in the kidney, which contributes to proteinuria.…”

Section: Discussionmentioning

confidence: 99%

“…Nestin expression was also detected in normal and pre-eclamptic placental tissues and in endothelial cells of the chorionic villi [8]. It has been reported that the expression of Nestin in the podocytes is low in nephropathy with proteinuria [9-11]. However, the relationship between the concentration of Nestin in urine samples and the progression of PE or its role in PE remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Yang¹,

Ding²,

Yang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that is characterised by a high incidence of hypertension and proteinuria. Podocytes are involved in the formation of a split membrane, which is the last barrier preventing the leakage of protein into the urine. Nestin, a cytoskeleton protein, is expressed stably in podocytes. However, the association between the Nestin concentration in urine and the progression of PE and the role of Nestin in PE remains unclear. Methods: In the present study, a mouse podocyte cell line, PE-like animal model and PE patients’ urine samples were used. Eilsa kits were used to detect the levels of proteins expression in urine samples from patients and animal models. Western Blotting and immunofluorescence were used to detect proteins expression levels in cell samples and animal tissue samples. Flow cytometry was used to detect the level of apoptosis in cells. Tunel assay was used to detect the levels of apoptosis in animal tissue samples. Results: Nestin levels were significantly increased in PE patients than in hypertensive patients and healthy subjects, and positively correlated with proteinuria and podocalyxin. Ang II treatment decreased the expression of Nestin and Podocin in a time- and dose- dependent manner in podocytes. Restoration of the Nestin levels could reverse Ang II-induced F-actin degradation and attenuate Ang II-mediated podocyte apoptosis, while knockdown of the Nestin level exhibited the opposite. Moreover, the protective role of Nestin on podocytes is mediated by inhibition of the kinase activity of CDK5. In PE-like animal model induced by L-NAME injection, restoration of Nestin lowered the pressure and proteinuria concentration, attenuated the loss of podocytes, and decreased the expression of p35, p53 and the activity of CDK5 kinase, as compared with the control. Conclusions: Our findings suggest that Nestin could improve preeclampsia-like symptoms by inhibiting the activity of CDK5, and Nestin may become a new prognostic factor and a potential therapy target for PE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Yang¹,

Ding²,

Yang³

et al. 2018

Kidney Blood Press Res

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“…In addition to these common histologic abnormalities, other glomerular abnormalities, such as segmental sclerosis, crescent formation, and adhesion to the Bowman capsules, are detected. Podocyte loss from the GBM in IgAN may cause or contribute to the progression of proteinuria, glomerulosclerosis, and filtration failure (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy

Asao

Asanuma

Kodama

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN).Design, setting, participants, & measurements Urine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA.Results Histologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P,0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22 Conclusions Levels of u-PCX and the number of urinary podocytes are associated with histologic abnormalities in adults with IgAN.

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“…Normopodocytic IgAN patients showed a significantly lower proteinuria progression rate than podocytopenic IgAN patients regardless of the comparable clinical features at biopsy and treatment regimen between the two groups. Podocyte injury is involved in development of proteinuria, and loss of podocytes predicts progression of proteinuria in IgAN [6]. More serious is that podocyte damage propagates injury by triggering secondary damage of "remnant" intact podocytes, even when the primary insult is shortlived.…”

Section: Introductionmentioning

confidence: 99%

Mesangial Medium from IgA Nephropathy Patients Induces Podocyte Epithelial-to-mesenchymal Transition through Activation of the Phosphatidyl Inositol-3-kinase/Akt Signaling Pathway

Wang

Liu

et al. 2012

Cell Physiol Biochem

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Background: Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis. Materials and Methods: Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes. Results: Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast –specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes. Conclusion: Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.

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Podocyte number predicts progression of proteinuria in IgA nephropathy

Cited by 42 publications

References 54 publications

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy

Mesangial Medium from IgA Nephropathy Patients Induces Podocyte Epithelial-to-mesenchymal Transition through Activation of the Phosphatidyl Inositol-3-kinase/Akt Signaling Pathway

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