Pirfenidone inhibits TGF-β1-induced fibrosis via downregulation of Smad and ERK pathway in MDCK cells.

Autor: Im CY; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Kim SH; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Song KH; Research Institute, ViroCure Inc., Seoul, Republic of Korea., Ryu MO; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Youn HY; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Seo KW; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. kwseo@snu.ac.kr.
Jazyk: angličtina
Zdroj: Veterinary research communications [Vet Res Commun] 2024 Oct; Vol. 48 (5), pp. 3167-3176. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1007/s11259-024-10493-y
Abstrakt: The prevalence of chronic kidney disease (CKD) in dogs increases with age, and renal fibrosis is an important pathophysiological mechanism in this process. However, only a few drugs that can effectively inhibit fibrosis in the kidneys of dogs are currently available. In this study, we aimed to determine whether pirfenidone, a drug that has shown antifibrotic effects in various clinical studies, also exerts antifibrotic effects on canine renal tubular epithelial cells, Madin-Darby canine kidney cells (MDCK). To this end, we treated MDCK cells with various concentrations of pirfenidone, followed by transforming growth factor-beta1 (TGF-β1) to stimulate fibrotic conditions. A cell viability assay was performed to determine the effect of pirfenidone on cell survival. Fibrosis-related markers and TGF-β1 fibrotic pathway-related markers were assessed using qPCR, Western blot analysis and immunocytochemistry. A one-way analysis of variance (ANOVA) was performed, followed by Tukey's post-hoc test for multiple comparisons. Pirfenidone treatment significantly reduced the expression of profibrotic markers such as α-smooth muscle actin, fibronectin, and collagen. Additionally, it upregulated the expression of E-cadherin, an epithelial marker. Furthermore, pirfenidone effectively inhibited the phosphorylation of key factors involved in the TGF-β1 signaling pathway, including Smad2/3 and ERK1/2. These results demonstrate that pirfenidone suppresses TGF-β1-induced fibrosis in MDCK cells by attenuating epithelial-mesenchymal transition and the relevant signaling pathways.
(© 2024. The Author(s).)
Databáze: MEDLINE
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