Chlorogenic Acid Inhibits Liver Fibrosis by Blocking the miR-21-Regulated TGF-β1/Smad7 Signaling Pathway in Vitro and in Vivo

Frontiers in Pharmacology

Juan Xue¹  Fan Yang²  Lei Zhao³  Xuan Zhou³  Zhi-Lin Chen³  Ying-Ying Luo⁴  Juan Zhang⁵  Yu-Jie Wang⁶  Yun-Fei Chen⁶  Zhi-De Zhu⁷  Yao Wang⁸  Pan Liu⁸  Xin Cai⁸  Lei Luo⁸  Qian Ma⁹ 

[1] Department of Gastroenterology, Hubei Provincial Hospital of Traditional Chinese and Western Medicine, Wuhan, China;Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Pulmonary Diseases, Jingmen City Hospital of Traditional Chinese Medicine, Jingmen, China;Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Guangxi University of Chinese Medicine, Nanning, China;School of Clinical Medical, Hubei University of Chinese Medicine, Wuhan, China;School of Life Sciences, Hubei University, Wuhan, China;

关键词: chlorogenic acid;    liver fibrosis;    TGF-β1;    miR-21;    Smad7;   

DOI  :  10.3389/fphar.2017.00929

来源: DOAJ

【 摘 要 】

Aims: Chlorogenic acid (CGA) is a phenolic acid that has a wide range of pharmacological effects. However, the protective effects and mechanisms of CGA on liver fibrosis are not clear. This study explored the effects of CGA on miR-21-regulated TGF-β1/Smad7 liver fibrosis in the hepatic stellate LX2 cell line and in CCl4-induced liver fibrosis in Sprague-Dawley rats.Methods: The mRNA expression of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase 1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and transforming growth factor-β1 (TGF-β1) and the protein levels of Smad2, p-Smad2, Smad3, p-Smad3, Smad2/3, p-Smad2/3, Smad7, CTGF, α-SMA, TIMP-1, MMP-9 and TGF-β1 were assayed in LX2 cells and liver tissue. The effects of CGA after miR-21 knockdown or overexpression were analyzed in LX2 cells. The liver tissue and serum were collected for histopathological examination, immunohistochemistry (IHC) and ELISA.Results: The mRNA expression of miR-21, CTGF, α-SMA, TIMP-1, and TGF-β1 and the protein expression of p-Smad2, p-Smad3, p-Smad2/3, CTGF, α-SMA, TIMP-1, and TGF-β1 were inhibited by CGA both in vitro and in vivo. Meanwhile, CGA elevated the mRNA and protein expression of Smad7 and MMP-9. After miR-21 knockdown and overexpression, the downstream molecules also changed accordingly. CGA also lessened the degree of liver fibrosis in the pathological manifestation and reduced α-SMA and collagen I expression in liver tissue and TGF-β1 in serum. Conclusion: CGA might relieve liver fibrosis through the miR-21-regulated TGF-β1/Smad7 signaling pathway, which suggests that CGA might be a new anti-fibrosis agent that improves liver fibrosis.

【 授权许可】

Unknown