Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

Wen, Duo; Li, You; Zhang, Qian; Zhang, Liying; Gu, Yong; Hao, Chuan‐Ming; Chen, Jing

doi:10.1159/000331701

Cited by 16 publications

(26 citation statements)

References 116 publications

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“…There was intense endothelial staining and a weaker appearance in the podocytes, which differed from previous reports using conventional preparation methods, in which nestin was expressed in terminally differentiated podocytes in mature kidneys [11,28,29]. Additionally, the immunolocalization of nestin in glomerular endothelial cells was obviously decreased under the acute hypertensive and cardiac arrest conditions.…”

Section: Resultscontrasting

confidence: 82%

Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions

Wang

Yin

et al. 2013

IJMS

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Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues were prepared by in vivo cryotechnique (IVCT). The distribution of glomeruli and podocyte proteins was visualized with DAB staining, confocal laser scanning microscopy and immunoelectron microscopy. The mRNA levels were examined by real-time quantitative PCR. The results showed the following: Under the normal condition, PCX stained intensely along glomerular epithelial cells, whereas nestin was clearly staining in the endothelial cells and appeared only weakly in the podocytes. Under the acute hypertensive and cardiac arrest conditions, PCX and nestin staining was not clear, with a disarranged distribution, but the colocalization of PCX and nestin was apparent under this condition. In addition, under the acute hypertensive and cardiac arrest conditions, the mRNA levels of PCX and nestin were significantly decreased. Collectively, the abnormal redistribution and decreased mRNA expressions of PCX and nestin are important molecular events at the early stage of podocyte injury during hemodynamic disorders. IVCT may have more advantages for morphological analysis when researching renal diseases.

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Section: Resultscontrasting

confidence: 82%

Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions

Wang

Yin

et al. 2013

IJMS

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“…It is reported that nestin expression of podocytes was significantly reduced in nephropathic patients with proteinuria (9). By contrast, in the puromycin aminonucleoside (PAN)-induced rat nephrosis model, nestin expression was up-regulated in the absence of podocyte apoptosis, even though the FP was significantly effaced (29). Increased nestin ex- …”

Section: Discussionmentioning

confidence: 99%

“…Independent of the underlying disease, the early events are character- Values are expressed as mean ± SD, *P < 0.05, **P < 0.01 compared with the age-matched WKY/Kpo pression could protect against apoptosis during PAN nephrosis and this process is mediated by maintaining the regular arrangement of the actin cytoskeleton (29). Of interest, CD2AP also inhibits the apoptosis of podocytes in albumin overload-induced endoplasmic reticulum (ER) stress (7).…”

Section: Discussionmentioning

confidence: 99%

<b>Characteristics of podocyte injury in malignant hypertensive nephropathy of rats (MSHRSP/Kpo </b><b>strain) </b>

2015

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Proteinuria is not only a hallmark of renal complication in malignant hypertension, but is also a major deteriorating factor for the progression to end-stage renal disease. Podocyte injury plays a crucial role in the renal damage associated with hypertensive nephropathy, but the underlying mechanism remains unclear. Malignant stroke-prone spontaneously hypertensive rats (MSHRSP/ Kpo) represent an original and useful model of human malignant hypertension. In this study, we disclosed the glomerular injuries in the MSHRSP/Kpo. MSHRSP/Kpo exhibited elevated blood pressure at 6 weeks along with renal dysfunction and proteinuria. Histological analysis of the MSHRSP/Kpo glomeruli revealed a severe atrophy, but no change was found in the podocyte number. The expression levels of podocyte-specific proteins, nephrin, podocin, and synaptopodin were decreased in the MSHRSP/Kpo glomeruli, though another podocyte-specific protein, CD2AP, in the MSHRSP/Kpo glomeruli exhibited a similar extent of staining as in normotensive WKY/ Kpo rats. Furthermore, desmin was not markedly detected in the WKY/Kpo glomeruli, but was strongly positive in MSHRSP/Kpo. By electron microscopy, well-formed foot processes (FP) were replaced by effacement in MSHRSP/Kpo. An original malignant hypertension strain MSHRSP/ Kpo exhibits podocyte injuries associated with the decrease of some podocyte-specific proteins and the upregulation of desmin, along with FP effacement and proteinuria.Malignant hypertension is critical for various kinds of vascular event and subsequent organ damage, such as stroke, cardiac hypertrophy, nephrosis, and atherosclerosis. Among these, hypertensive nephrosclerosis from long-standing uncontrolled hypertension is a major cause of chronic kidney disease and accounts for significant mortality (3). The histological lesions of hypertensive nephrosclerosis are well recognized and characterized by hyalinization and sclerosis of interlobular and afferent arterioles, together with tubulointerstitial fibrosis, glomerulosclerosis, and tubular cell atrophy (26). A number of factors including a defective renal autoregulatory response to hypertension, renal susceptibility genes, and environmental factors such as salt, smoking, and lead exposure have been suggested to contribute to the development of hypertensive nephrosclerosis (17). In particular, proteinuria is not only a hallmark of renal complication in hypertension, but is also a major deteriorating factor for the progression to endstage renal diseases (23,24). Glomerular epithelial cells, podocytes, which are located on the outside of the glomerulus and cover the capillary wall, play an important role in the glomerular filtration of the kidney. The podocytes do not proliferate after birth under normal conditions and are terminally differentiated to maintain an intricate and polarized cellular organization consisting of a cell body, major processes, and foot process

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“…Moreover, restoration of the Nestin level attenuated the Ang II-mediated apoptosis of podocytes. Previous studies have showed that knocking down Nestin expression resulted in a remarkable derangement of the actin cytoskeleton and an increase in apoptosis in cultured podocytes 24 h after being incubated with puromycin aminonucleoside, while up-regulation of the Nestin expression during puromycin aminonucleoside-induced nephrosis could protect the podocytes from apoptosis, this process was mediated by maintaining the regular arrangement of the actin cytoskeleton [16]. Thus, Nestin may play a protective role for the podocytes under hypertensive conditions.…”

Section: Discussionmentioning

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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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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Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

Cited by 16 publications

References 116 publications

Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions

Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions

<b>Characteristics of podocyte injury in malignant hypertensive nephropathy of rats (MSHRSP/Kpo </b><b>strain) </b>

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

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