Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy
文献类型：期刊论文
| 作者 | So, Wing Yan6; Liao, Yilie4,5,6; Liu, Wai Nam6; Rutter, Guy A.1,2,3; Han, Weiping6 |
| 刊名 | EMBO MOLECULAR MEDICINE
 |
| 出版日期 | 2023-11-07 |
| 页码 | 20 |
| 关键词 | AAV beta cells diabetes islet transplant PAX6 |
| ISSN号 | 1757-4676 |
| DOI | 10.15252/emmm.202317928 |
| 通讯作者 | So, Wing Yan(so_wing_yan@imcb.a-star.edu.sg) ; Han, Weiping(wh10@cornell.edu) |
| 英文摘要 | Loss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declined beta cell mass. Thus, strategies to preserve beta cells are imperatively needed. In this study, we identified paired box 6 (PAX6) as a critical regulator of beta cell survival. Under diabetic conditions, the human beta cell line EndoC-beta H1, db/db mouse and human islets displayed dampened insulin and incretin signalings and reduced beta cell survival, which were alleviated by PAX6 overexpression. Adeno-associated virus (AAV)-mediated PAX6 overexpression in beta cells of streptozotocin-induced diabetic mice and db/db mice led to a sustained maintenance of glucose homeostasis. AAV-PAX6 transduction in human islets reduced islet graft loss and improved glycemic control after transplantation into immunodeficient diabetic mice. Our study highlights a previously unappreciated role for PAX6 in beta cell survival and raises the possibility that ex vivo PAX6 gene transfer into islets prior to transplantation might enhance islet graft function and transplantation outcome. imagePAX6 was identified as a critical regulator of beta cell function, survival, and identity. Furthermore, PAX6 gene delivery in beta cells promoted beta cell potency, preserved beta cells, and enhanced the capability of glycemic control.PAX6 was down-regulated in beta cells under diabetic conditions.PAX6 regulated insulin and incretin signaling in beta cells.AAV-PAX6 administration in STZ-induced diabetic mice and db/db mice preserved beta cells and ameliorated glycemic disturbance.AAV-PAX6 transduction in human islets prior to transplantation preserved post-transplant islet graft and improved glycemic control in diabetic mice. PAX6 was identified as a critical regulator of beta cell function, survival, and identity. Furthermore, PAX6 gene delivery in beta cells promoted beta cell potency, preserved beta cells, and enhanced the capability of glycemic control.image |
| WOS关键词 | HUMAN PANCREATIC-ISLETS ; TRANSCRIPTION FACTORS ; DIABETES-MELLITUS ; PAX6 MUTATION ; TYPE-2 ; INSULIN ; DEDIFFERENTIATION ; MASS ; PROLIFERATION ; IDENTITY |
| 资助项目 | Research in the WHapos;s laboratory is supported by the Agency for Science, Technology and Research (A*STAR) Use-Inspired Basic Research Award, A*STAR Strategic Research Program (the Brain-Body initiative, iGrants call ID #21718) and the Biomedical Resear[21718] ; Agency for Science, Technology and Research (A*STAR) Use-Inspired Basic Research Award, A*STAR Strategic Research Program (the Brain-Body initiative) ; Biomedical Research Council core fund[NMRC/OFYIRG/066/2018-00] ; Young Individual Research Grant ; National Medical Research Council, Singapore ; scientific research funding of Human Resources and Social Security Bureau of Guangzhou City[212625/Z/18/Z] ; Wellcome Trust[MR/R022259/1] ; MRC Programme grant[BDA/11/0004210] ; MRC Programme grant[BDA/15/0005275] ; MRC Programme grant[BDA 16/0005485] ; Diabetes UK ; CRCHUM ; Innovation Canada |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001095504900001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307757]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | So, Wing Yan; Han, Weiping |
| 作者单位 | 1.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore 2.Imperial Coll London, Sect Cell Biol & Funct Genom, Div Diabet Endocrinol & Metab, Dept Metab Digest & Reprod,Fac Med, London, England 3.Univ Montreal, Fac Med, Ctr Rech CHUM, Montreal, PQ, Canada 4.Ctr Neurometab & Regenerat Med, Bioland Labs, Guangzhou 510530, Guangdong, Peoples R China 5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China 6.ASTAR, Agcy Sci Technol & Res, Inst Mol & Cell Biol IMCB, Singapore, Singapore |
| 推荐引用方式 GB/T 7714 | So, Wing Yan,Liao, Yilie,Liu, Wai Nam,et al. Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy[J]. EMBO MOLECULAR MEDICINE,2023:20. |
| APA | So, Wing Yan,Liao, Yilie,Liu, Wai Nam,Rutter, Guy A.,&Han, Weiping.(2023).Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy.EMBO MOLECULAR MEDICINE,20. |
| MLA | So, Wing Yan,et al."Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy".EMBO MOLECULAR MEDICINE (2023):20. |
入库方式： OAI收割
来源：上海药物研究所
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