[Relationship of mitogen-activated protein kinases activation with transdifferentiation of renal tubular epithelial cells in patients with IgA nephropathy]

Abstract

Objective: To investigate the expression patterns of MAPK family (including ERK, JNK and p38) and to analyze the effects of MAPKs on renal tubular epithelial cells (RTEC) transdifferentiation in vivo.

Methods: Renal biopsy specimen were collected from 36 patients with IgA nephropathy (IgAN), which were divided into mild proliferation group (MP), focal proliferation group (FP) and proliferation-sclerosis group (PS) according to the glomerular lesions. Renal tubulointerstitial lesion score was assessed. Positive tubules of PCNA, FN, alpha-SMA, MAPK subtypes expression and phosphorylation in renal tubules were detected by immunohistochemistry staining combined with semi-quantitative method. A correlation analysis was made.

Results: In the MP, FP and PS groups of IgAN, the score of tubulointerstitial lesion, the positive stained tubule of PCNA, alpha-SMA and FN expression were more abundant with the severity of glomerular injury. The expression of alpha-SMA in tubule was correlated closely to FN expression and the score of interstitial fibrosis. Distribution of all subtypes of MAPK in renal tissue was no different between IgAN and normal subjects. With the severity of glomerular disease, positive tubules expressed P-ERK or P-JNK increased gradually, especially in PS group, in which expression of P-ERK was 3 fold and P-JNK was 1.6 fold compared to control (P < 0.05). Expression of JNK protein in tubule was enhanced in PS group. Expression of P-p38 had no change in different groups. P-ERK positive tubules correlated to FN expression.

Conclusion: ERK and JNK are strongly expressed and activated in renal tubules in patients with IgAN. It seems that JNK activation is a critical signal to regulate RTEC transdifferentiation, but ERK activation may play an indirect role on this process.