A novel experimental mouse model of diabetic nonalcoholic steatohepatitis: A critical role for acid-sensitive Ion Channel 1a
文献类型：期刊论文
| 作者 | Hu, Xiaojie8; Lin, Huimin7; Qian, Shengying5,6; Xu, Zhou8; Li, Zihao8; Qian, Shishun8; Yang, Furong8; Hou, Hui4; Xie, Qinxiu3; Wu, Wenyong2 |
| 刊名 | BIOMEDICINE & PHARMACOTHERAPY
 |
| 出版日期 | 2024-09-01 |
| 卷号 | 178页码:15 |
| 关键词 | ASIC1a FPC Liver fibrosis NASH T2DM |
| ISSN号 | 0753-3322 |
| DOI | 10.1016/j.biopha.2024.117184 |
| 通讯作者 | He, Yong(heyong@simm.ac.cn) ; Huang, Yan(aydhy@126.com) |
| 英文摘要 | Background: A two-way relationship exists between type 2 diabetes (T2DM) and human nonalcoholic steatohepatitis (NASH). Several diabetic NASH models have the disadvantages of long cycles or inconsistent with the actual incidence of human disease, which would be costly and time-consuming to investigate disease pathogenesis and develop drugs. Therefore, there is an urgent need to establish a diabetic NASH mouse model. Methods: The combination between Fructose-palmitate-cholesterol diet (FPC) and Streptozotocin (STZ) (FPC+STZ) +STZ) was used to construct diabetic NASH mouse model. The in vivo effects of silencing acid-sensitive Ion Channel 1a (ASIC1a) were examined with an adeno-associated virus 9 (AAV9) carrying ASIC1a short hairpin RNA (shRNA) in FPC+STZ +STZ model. Results: The mice fed with FPC for 12 weeks had insulin resistance, hyperinsulinemia, lipid accumulation, and increased hepatic levels of inflammatory factors. However, it still did not develop remarkable liver fibrosis. Most interestingly, noticeable fibrotic scars were observed in the liver of mice from FPC+STZ +STZ group. Furthermore, insulin therapy significantly ameliorated FPC+STZ-induced +STZ-induced NASH-related liver fibrosis, indicating that hyperglycemia is of great significance in NASH development and progression. Importantly, ASIC1a was found to be involved in the pathogenesis of diabetic NASH as demonstrated that silencing ASIC1a in HSCs significantly ameliorated FPC+STZ-induced +STZ-induced NASH fibrosis. Mechanistically, ASIC1a interacted with Poly Adp-adenosine ribose polymerase (PARP1) to promote HSC activation by inducing autophagy. Conclusion: A FPC diet combined with an injection of STZ induces a diabetic NASH mouse model in a shorter period. Targeting ASIC1a may provide a novel therapeutic target for the treatment of diabetic NASH. |
| WOS关键词 | CHOLINE-DEFICIENT DIET ; LIVER FIBROSIS ; AUTOPHAGY ; INFLAMMATION ; DISEASE ; PROGRESSION ; ACTIVATION ; OBESITY |
| 资助项目 | National Natural Science Foundation of China[82370591] ; Natural Science Foundation of Hefei[2023018] ; Scientific Research Project of Higher Education Institutions in Anhui Province[2023AH040078] ; Design and transformation application of self-assembled nanomaterials based on active peptides of anti-liver fibrosis Clinical Medicine[H2023031] ; Scientific research level improvement plan of Anhui Medical University[2023xkjT010] ; The 2023 New Era Education Provincial Quality Engineering Project[2023lhpysfjd023] ; Scientific Research Platform Improvement Project of Anhui Medical University[2022xkjT04] ; The 2021 Anhui Province academic and Technology Leader candidate scientific research activities[2021H271] ; Anhui Medical University Basic and Clinical Cooperative Research Promotion Project[2019xkjT015] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001296174700001 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312887]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | He, Yong; Huang, Yan |
| 作者单位 | 1.Anhui Med Univ, Sch Int Educ, Hefei, Peoples R China 2.Hosp Second Peoples Hosp Anhui Prov, Hefei, Peoples R China 3.Anhui Med Univ, Dept Infect, Affiliated Hosp 1, Hefei, Peoples R China 4.Anhui Med Univ, Dept Gen Surg, Affiliated Hosp 2, Hefei, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Shanghai, Peoples R China 7.Anhui Med Univ, Dept Pharm, Affiliated Hosp 2, Hefei, Peoples R China 8.Anhui Med Univ, Sch Pharm, Anhui Prov Key Lab Major Autoimmune Dis, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Xiaojie,Lin, Huimin,Qian, Shengying,et al. A novel experimental mouse model of diabetic nonalcoholic steatohepatitis: A critical role for acid-sensitive Ion Channel 1a[J]. BIOMEDICINE & PHARMACOTHERAPY,2024,178:15. |
| APA | Hu, Xiaojie.,Lin, Huimin.,Qian, Shengying.,Xu, Zhou.,Li, Zihao.,...&Huang, Yan.(2024).A novel experimental mouse model of diabetic nonalcoholic steatohepatitis: A critical role for acid-sensitive Ion Channel 1a.BIOMEDICINE & PHARMACOTHERAPY,178,15. |
| MLA | Hu, Xiaojie,et al."A novel experimental mouse model of diabetic nonalcoholic steatohepatitis: A critical role for acid-sensitive Ion Channel 1a".BIOMEDICINE & PHARMACOTHERAPY 178(2024):15. |
入库方式： OAI收割
来源：上海药物研究所
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