Alpha-mangostin alleviate renal interstitial fibrosis via suppression of TGF-β1/Smad/ERK signaling axis in vitro and in vivo.

Abstract

α-mangostin (α-MG), a natural derivative of coumarin, exhibits anti-inflammatory, antioxidant and anti-fibrotic effects. This study aimed to determine the effect of α-MG treatment in mediating the process of renal interstitial fibrosis. We found that α-MG could alleviate tubule-interstitial damage and decrease fibrotic (α-smooth muscle actin [α-SMA], fibronectin, and collagen I), and epithelial-mesenchymal transition (EMT) protein (N-cadherin, Snail, Slug, TGF-β1 and vimentin) expression in unilateral ureteral obstruction (UUO) mice with chronic kidney disease. α-MG significantly decreased motility as well as inhibited expression of fibrotic- and EMT-related proteins in TGF-β1-induced HK2 cells. To clarify the molecular mechanisms of α-MG in reducing renal interstitial fibrosis, we used a MEK inhibitor (U0126) or Smad inhibitor (SB431542) cotreatment with α-MG. This is the first study is to demonstrate the antifibrotic effects of α-MG by targeting the TGF-β1/ERK/Smad-mediated EMT signaling pathway, is even more effective against renal interstitial fibrosis.

• Authors: Ying-Hsu Juan, Yung-Luen Yu, Yuan-Pei Tsai, Chu-Che Lee, Yong-Syuan Chen, Yi-Hsuan Ting, Jen-Pi Tsai, Yi-Hsien Hsieh
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 218 Pg. 115935 (12 2023) ISSN: 1873-2968 [Electronic] England
• PMID: 37989414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• mangostin
• Transforming Growth Factor beta1
• Smad Proteins

Topics

• Mice
• Animals
• Transforming Growth Factor beta1 (metabolism)
• Smad Proteins (metabolism)
• Signal Transduction
• Ureteral Obstruction (metabolism, pathology)
• Renal Insufficiency, Chronic (metabolism)
• Fibrosis
• Epithelial-Mesenchymal Transition
• Kidney (metabolism)