Down-regulation of nestin expression in the glomeruli with foot process effacement and its correlation with the degree of proteinuria / 中华肾脏病杂志

ABSTRACT

Objective To investigate the expression of nestin, a type Ⅵ intermediate filament protein in the glomeruli with foot process effacement and the potential relationship between nestin expression in the kidney and the degree of proteinuria. Method Immunohistochemistry was used to determine the localization of nestin in the kidney samples obtained from needle biopsies of normal human and patients with minimal change disease (MCD). Puromycin aminonucleoside (PAN) nephrosis rat models were established by a single intraperitoneal injection of PAN. Both real time quatitative reverse PCR and Western blot methods were applied to evaluate the levels of nestin expression at day 1, 4, 10 and 20 after PAN injection. Results Immunohistochemistry showed that the expression of nestin in glomeruli of MCD patients was significantly reduced compared with normal samples (0.93±0.08 vs 1.65±0.12, P<0.05) . The mRNA and protein expressions of nestin in the rat kidney were transitorily increased by 1.23 folds and 1.48 folds of control group (NC) after 1 day of PAN injection (P<0.05), then decreased quickly in the following days. The mRNA levels of nestin in the kidney were 35.8% and 12.1% of NC after 4 days and 10 days of PAN injection, respectively, (P<0.01) as determined by real time PCR. After 20 days of PAN injury, nestin mRNA expression partly recovered to 65.8% of NC (P< 0.05 ). The protein levels of nestin detected by Western blot presented the similar trend, which were 77.0%, 58.0% and 83.4% of NC after 4 days, 10 days and 20 days of PAN injection, respectively (P<0.05). The degree of proteinuria in puromycin aminonucleoside nephrosis rats was negatively correlated with both mRNA and protein levels of nestin in the kidney(r=-0.667,P<0.05 and r=-0.621 ,P<0.05, respectively). Conclusions The expression of intermediate filament protein nestin is down-regnlated in the kidney characterized with foot process effacement and negatively correlated with the degree of proteinuria in puromycin aminonucleoside nephrosis rats. Nestin may play a potential role in modulating the structure and function of podocyte.