MiR‐126‐3p and MiR‐195‐5p as Novel Therapeutic Attenuators of Liver Fibrosis by Targeting the IRS1/PI3K Signalling Pathway

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Publicado en:Liver International vol. 45, no. 10 (Oct 2025)
Autor principal: Yuan, Xia
Otros Autores: Zhang, Kun, Wang, Dan, Li, Jie, Lyu, Peng, Zhao, Xuemei, Zhang, Kang, Li, Hongting, Liu, Bo, Ma, Liping
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LEADER 00000nab a2200000uu 4500
001 3254042899
003 UK-CbPIL
022 |a 1478-3223 
022 |a 1478-3231 
024 7 |a 10.1111/liv.70302  |2 doi 
035 |a 3254042899 
045 2 |b d20251001  |b d20251031 
100 1 |a Yuan, Xia  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
245 1 |a MiR‐126‐3p and MiR‐195‐5p as Novel Therapeutic Attenuators of Liver Fibrosis by Targeting the IRS1/PI3K Signalling Pathway 
260 |b Wiley Subscription Services, Inc.  |c Oct 2025 
513 |a Journal Article 
520 3 |a Background & Aims Hepatic fibrosis is a progressive response to chronic liver injury. A key event in the development of hepatic fibrosis is the activation of hepatic stellate cells (HSCs); emerging research indicates that microRNAs play crucial roles in regulating HSCs activation. However, the specific roles of miR‐126‐3p (miR‐126) and miR‐195‐5p (miR‐195) in liver fibrosis remain inadequately understood. Methods We examined the expression of miR‐126 and miR‐195 in activated HSCs, fibrotic liver tissues from animal models, and blood samples from patients with liver disease. The effects on cell proliferation and migration were investigated by MTT, colony formation assay, cell wound healing assay, and Transwell assay. Finally, we evaluated the effect of miR‐126 and miR‐195 on the progression of liver fibrosis in mice. Results We revealed that miR‐126 and miR‐195 were markedly downregulated in activated HSCs, fibrotic liver tissues from animal models, and blood samples from patients with liver diseases. Functional experiments demonstrated that the overexpression of miR‐126 and miR‐195 significantly inhibited the proliferation, migration, and fibrotic markers expression in HSCs. Conversely, silencing miR‐126 and miR‐195 produced the opposite effects. Further mechanistic studies showed that miR‐126 and miR‐195 downregulate insulin receptor substrate 1 (IRS1) or phosphoinositide 3‐kinase regulatory subunit 2 (PIK3‐R2), respectively, thereby inhibiting the pro‐fibrotic signalling pathway (IRS1/PI3K) and regulating the functions of HSCs. Importantly, in vivo experiments demonstrated that miR‐126 and miR‐195 markedly alleviated CCL4‐induced hepatic fibrosis in mice. Conclusions Our results unravel that miR‐126 and miR‐195 inhibit liver fibrosis by suppressing the IRS/PI3K pathway. 
653 |a Liver 
653 |a Blood 
653 |a Fibrosis 
653 |a Kinases 
653 |a miRNA 
653 |a Assaying 
653 |a Cell proliferation 
653 |a Wound healing 
653 |a Animal models 
653 |a Stellate cells 
653 |a 1-Phosphatidylinositol 3-kinase 
653 |a Cell migration 
653 |a Liver cirrhosis 
653 |a Down-regulation 
653 |a Insulin receptor substrate 1 
653 |a Liver diseases 
653 |a Signal transduction 
653 |a Cell activation 
700 1 |a Zhang, Kun  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Wang, Dan  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Li, Jie  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Lyu, Peng  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Zhao, Xuemei  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Zhang, Kang  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Li, Hongting  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
700 1 |a Liu, Bo  |u The 3rd Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital of Chengdu, Chengdu, Sichuan, People's Republic of China 
700 1 |a Ma, Liping  |u Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China 
773 0 |t Liver International  |g vol. 45, no. 10 (Oct 2025) 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3254042899/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch