2. Academic Validation
  3. Inhibition of miR-431-5p attenuated liver apoptosis through KLF15/p53 signal pathway in S100 induced autoimmune hepatitis mice

Inhibition of miR-431-5p attenuated liver apoptosis through KLF15/p53 signal pathway in S100 induced autoimmune hepatitis mice

  • Life Sci. 2021 Sep 1;280:119698. doi: 10.1016/j.lfs.2021.119698.
Yulu Tu 1,  Dazhi Chen 2,  Tongtong Pan 1,  Zhengkang Chen 1,  Jie Xu 1,  Lanling Jin 1,  Lina Sheng 3,  Xiaozhi Jin 1,  Xiaodong Wang 1,  Xiaolin Lan 4,  Yuli Ge 5,  Huiling Sun 6,  Yongping Chen 7
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325006, China.
  • 2 Department of Gastroenterology, The First Hospital of Peking University, Beijing 100032, China.
  • 3 Department of Infectious Diseases, The Affiliated Yiwu Central Hospital of Wenzhou Medical University, Yiwu 322000, China.
  • 4 Department of Infectious Diseases, Lishui People's Hospital, Lishui 323000, China.
  • 5 Department of Infectious Diseases, Lishui People's Hospital, Lishui 323000, China. Electronic address: yuli_ge@163.com.
  • 6 Department of Infectious Diseases, Lishui People's Hospital, Lishui 323000, China. Electronic address: huiling__sun01@163.com.
  • 7 Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325006, China. Electronic address: cyp@wmu.edu.cn.
PMID: 34111466 DOI: 10.1016/j.lfs.2021.119698
Abstract

Aims: The purpose of this study was to investigate the effects of miR-431-5p on hepatocyte Apoptosis in AIH.

Materials and methods: We used intraperitoneal injection of S100 to establish AIH mouse model and injected AAV into tail vein on day 14 of modeling to regulate miR-431-5p expression. The expression of ALT, AST, IgG and apoptosis-related proteins Bax, Bcl-2 and cleaved Caspase 3 were measured in each group. Cellular experiments were performed using miR-431-5p mimics or inhibitors to transfect LPS-stimulated AML12 cells, and Apoptosis was verified using Western blot and Hoechst 33342/PI Double Staining. The target of miR-431-5p, KLF15, was screened using databases and verified by the luciferase reporter assay. The relationship between KLF15 and p53 was verified by si-KLF15 and PFTβ (a p53-specific inhibitor).

Key findings: Here, we observed that the increase in the level of miR-431-5p was accompanied by a decrease in the expression of Krüppel-like zinc finger transcription factor 15 (KLF15). In addition, the deletion of miR-431-5p significantly reduced hepatocyte Apoptosis in AIH mice induced by liver S100 and Apoptosis of AML12 cells induced by LPS stimulation, accompanied by decreased expression of Bax and cleaved Caspase-3 as well as increased expression of Bcl-2. Moreover, KLF15 was the direct and functional target of miR-431-5p. Furthermore, miR-431-5p negatively regulated the expression of KLF15, and KLF15 deletion partially abolished the inhibitory effect of miR-431-5p deletion on Apoptosis by activating p53 signaling.

Significance: In summary, miR-431-5p may be a potential therapeutic target for AIH.

Keywords

Apoptosis; Autoimmune hepatitis; Krüppel-like factor 15 (KLF15); miR-431; p53.

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