Master's course Seoul National University Seoul, Seoul-t'ukpyolsi, Republic of Korea
Background: 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. Pirfenidone is an FDA-approved drug for human idiopathic pulmonary fibrosis (IPF) which has shown antifibrotic effects in various animal clinical studies. Hypothesis/
Objectives: Antifibrotic effects of pirfenidone on canine renal tubular epithelial cells (MDCK) were evaluated. Animals: This is an in vitro experiment using a canine MDCK cell line.
Methods: MDCK cells were treated 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.
Results: Pirfenidone significantly reduced the expression of profibrotic markers such as α-smooth muscle actin (α-SMA), 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 pathway, including Smad2/3 and ERK1/2. Conclusions and clinical importance: These results demonstrate that pirfenidone modulates TGF-β1-induced fibrosis in MDCK cells by attenuating key TGF-β1 signaling pathways. These findings highlight the potential of pirfenidone as a therapeutic agent in the treatment of renal fibrosis in end-stage CKD in dogs after further in vivo research.
