Key result
Treatment with lisinopril or pyrvinium pamoate decreased renal fibrosis markers and β-catenin target genes in 2K1C hypertensive rats, implicating the β-catenin pathway in renal fibrosis.
Why the study?
Does inhibition of the β-catenin signaling pathway reduce renal fibrosis in a rat model of hypertension?
Does inhibition of the β-catenin signaling pathway reduce renal fibrosis in a rat model of hypertension?
Absolute Event Rate: 112% vs 220%
p-value: p=<0.05
The β-catenin-dependent signaling pathway contributes to hypertension-induced renal fibrosis, and its inhibition reduces fibrotic markers independent of blood pressure reduction.
Hypothesis-generating for β-catenin inhibition in hypertensive renal fibrosis; prospective human studies needed before clinical adoption.
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.
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Cuevas et al. (2015) studied Hypertension-induced renal fibrosis. Lisinopril or pyrvinium pamoate vs. Untreated 2K1C rats was evaluated on Systolic blood pressure (p=<0.05). Treatment with lisinopril or pyrvinium pamoate decreased renal fibrosis markers and β-catenin target genes in 2K1C hypertensive rats, implicating the β-catenin pathway in renal fibrosis.
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