Abstract
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.
Highlights
Hypertension is a major risk factor for development and progression of chronic kidney disease [1]
Animals were randomly divided into four groups (4 animals per group) according to the treatment: sham operated control, 2K1C rats without treatment, 2K1C rats treated with lisinopril (10 mg/kg/day) by oral gavage for four weeks starting from fourth week after surgery, and 2K1C rats treated with pyrvinium pamoate (60 μg/kg, single dose every 3 days) by oral gavage for 2 weeks starting from sixth week after surgery
The Systolic blood pressure (SBP) significantly decreased in rats treated for 4 weeks with lisinopril compared with 2K1C rats without treatment (112 ± 5 versus 220 ± 4 mmHg, P < 0.05) (Figure 1)
Summary
Hypertension is a major risk factor for development and progression of chronic kidney disease [1]. The main consequence of the untreated hypertension is the chronic renal injury including vascular, glomerular, and tubulointerstitial injuries. Renal fibrosis is a hallmark of chronic hypertensive disease. In animals and patients with chronic hypertension, the decline on renal function is correlated with the degree of renal fibrosis leading to end-organ failure [2]. Studies using the model of Ang IIdependent hypertension have showed extensive glomerular and tubulointerstitial fibrosis [4]. It has been shown that the hypertension induced in 2K1C Goldblatt model is a consequence of increase in tissue Ang II content in both acute and chronic 2K1C animals [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
