Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy

Tomioka, Mai; Hiromura, Keiju; Sakairi, Toru; Takeuchi, Sora; Maeshima, Akito; Kaneko, Yoriaki; Kuroiwa, Takashi; Takeuchi, Toshiyuki; Nojima, Yoshihisa

doi:10.1111/j.1440-1797.2010.01342.x

Cited by 27 publications

(34 citation statements)

References 27 publications

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“…By using samples of patients with crescentic glomerulonephritis, Thorner et al [33] found that nestin was detected in more than 50% of the crescents in the renal species. In the study by Tomioka et al [34], expression of nestin was increased in the tubulointerstitium of patients with IgA nephropathy, whilst in normal kidney it was hardly detected in the tubulointerstitium. A further study demonstrated that peritubular endothelial cells and tubulointerstitial myofibroblasts expressed nestin during the progression of tubulointerstitial injury and nestin expression was associated with deterioration of renal function.…”

Section: Discussionmentioning

confidence: 99%

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Zhang

Chen

et al. 2014

Am J Nephrol

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Objectives: Acute kidney injury (AKI) is a common complication in hospitalized patients and the incidence of AKI is rapidly increasing. Despite the advances in treatment of AKI, many patients still progress to end-stage renal disease and depend on dialysis. Therefore, early diagnosis and adequate treatment of AKI could improve prognosis. Methods: We established rat models of AKI induced by cisplatin nephrotoxicity and renal ischemia-reperfusion (I/R). Urine samples were collected, labeled with isobaric tags for relative and absolute quantification agents, and then subjected to nano-LC-MS/MS-based proteomic analysis. Results of the proteomic study were confirmed by Western blot. We also performed RNAi to silence nestin and investigate its role in renal I/R injury. We then validated its clinical application by studying urine nestin levels in AKI patients with cardiovascular surgeries. Results: Our proteomic analysis showed that fetuin-A, nestin, hamartin and T-kininogen were differentially expressed in the urine samples of rats after cisplatin or I/R treatment. Western blot confirmed the differential expression of these proteins in animal models and ELISA confirmed the differential expression of nestin in human urine samples. To explore the expression of nestin in the development of AKI, our results showed that nestin was primarily detected in the glomeruli and barely detected in tubular cells but increased in tubular cells during I/R- and cisplatin-induced AKI. The urine nestin-to-creatinine ratio increased earlier than serum creatinine in AKI patients with postcardiovascular surgeries. The role of nestin in AKI might be related to the p53 signaling pathway. Conclusions: Thus, our results demonstrated that urinary nestin could be a urinary biomarker for patients with AKI and its role in AKI might be related to the p53 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Zhang

Chen

et al. 2014

Am J Nephrol

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“…Furthermore, the number of nestin/smooth muscle ␣-actin ϩ cells identified in the damaged kidney positively correlated with fibrosis (46). In 2010, Tomioka and colleagues (52) reported an analogous paradigm in the injured human kidney secondary to immunoglobulin A nephropathy as nestin was detected in a subpopulation of smooth muscle ␣-actin ϩ myofibroblasts. Tomioka et al (52) further demonstrated that nestin expression positively correlated with tubulointerstitial fibrosis, and patients with higher levels of the intermediate filament protein were associated with a significant worsening of renal function.…”

Section: Nestin Expression In Endothelial Cells and Myofibroblastsmentioning

confidence: 99%

“…In 2010, Tomioka and colleagues (52) reported an analogous paradigm in the injured human kidney secondary to immunoglobulin A nephropathy as nestin was detected in a subpopulation of smooth muscle ␣-actin ϩ myofibroblasts. Tomioka et al (52) further demonstrated that nestin expression positively correlated with tubulointerstitial fibrosis, and patients with higher levels of the intermediate filament protein were associated with a significant worsening of renal function. Therefore, injury to the heart and kidney is associated with the appearance of a subpopulation of nestin/smooth muscle ␣-actin ϩ myofibroblasts.…”

Section: Nestin Expression In Endothelial Cells and Myofibroblastsmentioning

confidence: 99%

Nestin⁺cells and healing the infarcted heart

Calderone

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…These data suggest that nestin may play an important role in maintaining the normal morphology and function of podocytes. Further, several studies have shown that nestin expression is induced in other types of renal parenchymal cells following renal injury, suggesting the potential role of nestin in repairing kidney damage [12,14,15,16,17,18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

Wen

Li²,

Zhang³

et al. 2011

Am J Nephrol

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Background: Nestin is an intermediate filament protein widely used as a marker of stem cells or progenitor cells. Nestin is also highly expressed in the glomerular podocyte, a type of terminally differentiated epithelial cell. Little is known about the significance of nestin in podocytes. Methods: Puromycin aminonucleoside (PAN) was injected into the rats to produce a PAN nephrosis model. Transmission electronic microscopy and terminal dUTP nick end-labeling assay were used to examine the podocyte foot process (FP) effacement and apoptosis, respectively. A mouse podocyte cell line was cultured and incubated with PAN. Immunoblot was used to examine the level of nestin expression both in vivo and in vitro. Enhanced green fluorescence protein-tagged plasmids containing nestin shRNA were transfected into the cultured podocytes to silence nestin expression. F-actin arrangement within cultured podocytes was investigated by immunofluorescence, while the apoptosis rate was examined by both Hoechst stain and flow cytometry. Results: In the PAN-induced rat nephrosis model, podocyte nestin expression was increased in the absence of apparent podocyte apoptosis, even though the FP was significantly effaced. In the cultured mouse podocytes, PAN upregulated nestin expression in a time-dependent manner within 24 h of treatment. Notably, no significant apoptosis occurred, however knocking down nestin expression resulted in a remarkable derangement of actin cytoskeleton and an increase in apoptosis in the cultured podocytes 24 h after being incubated with PAN. Conclusions: Upregulation of nestin expression during PAN nephrosis could protect podocytes from apoptosis and that this process is mediated by maintaining the regular arrangement of actin cytoskeleton.

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Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy

Abstract: Nestin expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis.

Cited by 27 publications

References 27 publications

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Nestin⁺cells and healing the infarcted heart

Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

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Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy

Abstract: Nestin expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis.

Cited by 27 publications

References 27 publications

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Nestin+cells and healing the infarcted heart

Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

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Nestin⁺cells and healing the infarcted heart