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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.
Meng, Hao; Liao, Zhiying; Ji, Yanting; Wang, Dong; Han, Yang; Huang, Chaolin; Hu, Xujuan; Chen, Jingyi; Zhang, Hengrui; Li, Zonghong; Wang, Changliang; Sun, Hui; Sun, Jiaqi; Chen, Lihua; Yin, Jiaxiang; Zhao, Jincun; Xu, Tao; Liu, Huisheng.
Afiliación
  • Meng H; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 511495, Guangdong, China.
  • Liao Z; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Ji Y; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 511495, Guangdong, China.
  • Wang D; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Han Y; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Huang C; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
  • Hu X; Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, 430023, Hubei, China.
  • Chen J; Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, 430023, Hubei, China.
  • Zhang H; Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, 430023, Hubei, China.
  • Li Z; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Wang C; School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, Guangdong, China.
  • Sun H; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Sun J; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Chen L; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Yin J; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Zhao J; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Xu T; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
  • Liu H; Guangzhou National Laboratory, Guangzhou, 510320, Guangdong, China.
Signal Transduct Target Ther ; 9(1): 104, 2024 Apr 23.
Article en En | MEDLINE | ID: mdl-38654010
ABSTRACT
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Islotes Pancreáticos / Factor 7 de Crecimiento de Fibroblastos / Enzima Convertidora de Angiotensina 2 / COVID-19 Límite: Animals / Humans / Male Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Islotes Pancreáticos / Factor 7 de Crecimiento de Fibroblastos / Enzima Convertidora de Angiotensina 2 / COVID-19 Límite: Animals / Humans / Male Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido