Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy
Abstract 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 s...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202317928 |
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| author | Wing Yan So Yilie Liao Wai Nam Liu Guy A Rutter Weiping Han |
| author_facet | Wing Yan So Yilie Liao Wai Nam Liu Guy A Rutter Weiping Han |
| author_sort | Wing Yan So |
| collection | DOAJ |
| description | Abstract 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‐βH1, 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. |
| format | Article |
| id | doaj-art-135e3d13ea6e412ba77f578d5de7bd63 |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-135e3d13ea6e412ba77f578d5de7bd632025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-11-01151212010.15252/emmm.202317928Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacyWing Yan So0Yilie Liao1Wai Nam Liu2Guy A Rutter3Weiping Han4Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Centre de Recherche du CHUM, Faculté de Médicine, Université de MontréalInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Abstract 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‐βH1, 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.https://doi.org/10.15252/emmm.202317928AAVbeta cellsdiabetesislet transplantPAX6 |
| spellingShingle | Wing Yan So Yilie Liao Wai Nam Liu Guy A Rutter Weiping Han Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy EMBO Molecular Medicine AAV beta cells diabetes islet transplant PAX6 |
| title | Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| title_full | Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| title_fullStr | Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| title_full_unstemmed | Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| title_short | Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| title_sort | paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy |
| topic | AAV beta cells diabetes islet transplant PAX6 |
| url | https://doi.org/10.15252/emmm.202317928 |
| work_keys_str_mv | AT wingyanso pairedbox6genedeliverypreservesbetacellsandimprovesislettransplantationefficacy AT yilieliao pairedbox6genedeliverypreservesbetacellsandimprovesislettransplantationefficacy AT wainamliu pairedbox6genedeliverypreservesbetacellsandimprovesislettransplantationefficacy AT guyarutter pairedbox6genedeliverypreservesbetacellsandimprovesislettransplantationefficacy AT weipinghan pairedbox6genedeliverypreservesbetacellsandimprovesislettransplantationefficacy |