Inhibition of miR-431-5p attenuated liver apoptosis through KLF15/p53 signal pathway in S100 induced autoimmune hepatitis mice
| Autor: | Xiao-Dong Wang, Jin Lanling, Lina Sheng, Hui-ling Sun, Yu-li Ge, Tongtong Pan, Jie Xu, Xiaolin Lan, Chen Zhengkang, Yulu Tu, Yong-Ping Chen, Jin Xiaozhi, Dazhi Chen |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Intraperitoneal injection Kruppel-Like Transcription Factors Down-Regulation Apoptosis Stimulation Caspase 3 KLF15 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine Western blot medicine Animals General Pharmacology Toxicology and Pharmaceutics Zinc finger transcription factor medicine.diagnostic_test Chemistry S100 Proteins General Medicine Transfection Molecular biology Up-Regulation Mice Inbred C57BL Disease Models Animal Hepatitis Autoimmune MicroRNAs 030104 developmental biology Liver Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Life Sciences. 280:119698 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2021.119698 |
| Popis: | 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 Kruppel-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. |
| Databáze: | OpenAIRE |
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