title: β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats.
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.
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.
authors.forename: Catherina A
authors.initials: CA
authors.lastname: Cuevas
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.
authors.forename: Cheril
authors.initials: C
authors.lastname: Tapia-Rojas
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cespedes
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile ; Center for Aging and Regeneration CARE-Chile UC, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile ; Center for Aging and Regeneration CARE-Chile UC, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
mesh_terms: D000804:Angiotensin II / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017706:Lisinopril / Q000008:administration & dosage; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011774:Pyrvinium Compounds / Q000008:administration & dosage; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics*
chemical_list: C530106:Ccnd1 protein, rat; D016271:Proto-Oncogene Proteins c-myc; D011774:Pyrvinium Compounds; D051176:beta Catenin; D000804:Angiotensin II; D019938:Cyclin D1; C024631:pyrvinium; D017706:Lisinopril