β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

Abstract EN

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect.

Since β -catenin signal transduction participates in fibrotic processes, we evaluated the contribution of β -catenin-dependent signaling pathway in hypertension-induced renal fibrosis.

Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks).

The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg ( P < 0.05 ), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg, P > 0.05 ).

The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats.

The expressions of β -catenin, p-Ser9-GSK-3beta, and the β -catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments ( P < 0.05 ).

In this study we provided evidence that β -catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.