Alpha-lipoic acid ameliorates the epithelial mesenchymal transition induced by unilateral ureteral obstruction in mice.

Abstract

The epithelial-to-mesenchymal transition (EMT) is one of mechanisms that induce renal interstitial fibrosis. Understanding EMT in renal fibrosis has important therapeutic implications for patients with kidney disease. Alpha-lipoic acid (ALA) is a natural compound with antioxidant properties. Studies for ALA are performed in acute kidney injury with renal tubular apoptosis, renal inflammation, and oxidative stress. We investigated the effects of ALA on EMT-mediated renal interstitial fibrosis in mice with unilateral ureteral obstruction (UUO). UUO mice developed severe tubular atrophy and tubulointerstitial fibrosis, with a robust EMT response and ECM deposition after 7 postoperative days. In contrast, ALA-treated UUO mice showed only moderate injury and minimal fibrosis and also larger reductions in the expression of ECM proteins, inflammatory factors, and EMT markers. ALA was shown to be involved in the suppression of infiltrating macrophages associated with EMT and the progression of interstitial fibrosis. It also lessened the destruction of the tubular basement membrane, by reducing the expression of matrix metalloproteinases. This is the first study to show that ALA modulates EMT in a UUO mouse model. Our results suggest that ALA merits further exploration as a therapeutic agent in the prevention and treatment of chronic kidney disease.

• Authors: Hyun Seop Cho, Jin Hyun Kim, Ha Nee Jang, Tae Won Lee, Myeong Hee Jung, Tae Ho Kim, Se-Ho Chang, Dong Jun Park
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 46065 (04 05 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28378840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Smad Proteins
• Transforming Growth Factor beta1
• Intercellular Adhesion Molecule-1
• Thioctic Acid
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Epithelial-Mesenchymal Transition (drug effects)
• Fibrosis
• Inflammation (pathology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Kidney (drug effects, pathology)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Signal Transduction
• Smad Proteins (metabolism)
• Thioctic Acid (pharmacology, therapeutic use)
• Transforming Growth Factor beta1 (metabolism)
• Ureteral Obstruction (drug therapy, enzymology, pathology)