Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 128, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110241
Keywords
Salvianolic acid B; Epithelial-mesenchymal transition; Chronic renal fibrosis; Autophagy; Sirt1
Funding
- National Natural Science Foundation of China [81974531, 81603371, 81673874, 81803824]
- National Natural Science Foundation of Guangdong Province [2016A030310292, 2018B0303110004, 2018A030313328]
- Education Department of Guangdong Province [2016KZDXM030]
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Renal fibrosis is a kind of progressive kidney disease leading to end-stage renal damage. Epithelial-mesenchymal transition (EMT) is one of the crucial features of renal fibrosis. Salvianolic acid B (SalB), isolated from traditional Chinese medicine Radix Salviae miltiorrhizae, has been proved to be suitable for renal protection. The aims of this study are to investigate the pharmacological effects of SalB on renal fibrosis and explore the underlying mechanisms. In vivo, our study showed that SalB could improve kidney dysfunction and reduce the expression of EMT-related proteins, including fibronectin (FN), alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta). In addition, SalB activated autophagy and up-regulated the expression of Sirt1. In vitro, our study showed that SalB reversed EMT in TGF-beta 1-induced human kidney proximal tubular epithelial cells (HK-2 cells). Further mechanism studies showed that the inhibition of Sirt1 and autophagy could reverse the protective effect of SalB on the EMT process in TGF-beta 1-induced HK-2 cells. Taken together, this study demonstrated that SalB attenuates EMT in the process of renal fibrosis through activating Sirt1-mediated autophagy, and Sirt1 could be a key target for treatment of renal fibrosis.
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