Early Activation of PINCH/ Glycogen-Synthase Kinase 3β/ERK Pathway in Obstructive Nephropathy Rat Model.

BACKGROUND: Despite a previous study showing that PINCH-1 exerts an important role in regulating TGF-β1-mediated mesenchymal transition through its interaction with integrin-linked kinase, relatively little is known about the role of PINCH in the obstructive nephropathy.

METHODS: To construct a rat model of renal interstitial fibrosis and obstructive nephropathy, unilateral ureteral obstruction (UUO) was used. Hematoxylin and eosin and Masson staining were used in histologic examinations. Quantificational reverse transcription-PCR was used to analyze the mRNA expression level. Western blot and the immunohistochemistry staining were used to detect the protein levels.

RESULTS: Histologic examination showed that slight interstitial fibrosis and tubular atrophy existed in the kidney of UUO rats. PINCH, alpha-smooth muscle actin, vascular endothelial growth factor and connective tissue growth factor were markedly induced in the kidney of the UUO rats. However, the expression level of E-cadherin was markedly suppressed in the kidney of the UUO rats. Moreover, both JUN and phosphorylation of JUN proteins were significantly decreased in the kidney of the UUO rats. Conversely, phosphorylation of ERK1/2 and glycogen-synthase kinase 3β (GSK3β) were markedly induced in UUO rats compared to that in sham rats. However, ERK1/2 proteins showed no statistically significant difference between UUO and sham groups.

CONCLUSIONS: PINCH/GSK3β/ERK pathway was early molecular responses to obstructed kidney induced by UUO in rat.