Embryonic stem cells-derived exosomes enhance retrodifferentiation of retinal Müller cells by delivering BDNF protein to activate Wnt pathway |
| |
| Institution: | 1. Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, PR China;2. Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Tianjin Medical University Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, PR China;3. Department of Cell Biology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, PR China;1. Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr. Bacelar 902, CEP 04057-000, São Paulo, SP, Brazil;2. Faculdade de Medicina da Universidade Federal de Alagoas, Campus A. C. Simões Tabuleiro do Martins, CEP 57072-900, Maceió, AL, Brazil;3. Departamento de Fisiopatologia, Instituto Butantan, Av. Vital Brasil 1500, CEP 05503-900, São Paulo, SP, Brazil;4. Pesquisadora associada, Pós-Doutoranda da Companhia Ambiental do Estado de São Paulo - CETESB, Brazil;1. Immunology Department, Medical School, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran;2. Asadabad School of Medical Sciences, Hamadan, Asadabad, Iran;3. Cellular and Molecular Research Center, Department of Immunology, Medical School, Birjand University of Medical Sciences, Ghafari Street, Birjand, Southern Khorasan, Iran;4. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran;5. Immunology Department, Medical School, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran;6. Department of Immunology, Medical School, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan 81746-73695, Iran;1. Department of Thoracic-cardiac Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, Hubei 430061, China;2. Hubei University of Chinese Medicine, Wuhan, Hubei 430061, China;3. ChosenMed Technology (Beijing) Co. Ltd, Beijing 100176, China;1. Department of Pediatrics, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China;2. Department of Pediatrics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China;3. Department of Pediatrics, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing 210093, Jiangsu, China;4. Department of Pediatrics, Jinling Hospital, Nanjing Medical University, Nanjing 210093, Jiangsu, China;1. Department of Anatomy, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;2. Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;3. Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;4. Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, 200025 Shanghai, China;2. Pôle de Recherches Sino-Français en Science du Vivant et Génomique, 197 Rui Jin Er Road, 200025 Shanghai, China;3. CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38700 La Tronche, France |
| |
| Abstract: | ObjectiveThe present study was intended to investigate the role of embryonic stem cell-derived exosomes (ESC-Exos) in Müller cell retrodifferentiation and their specific mechanism.MethodsFollowing co-incubation of the extracted ESC-Exos and Müller cells, their effects on the retrodifferentiation and proliferation of Müller cells were measured by EdU staining, immunofluorescence, and western blot. ESCs transfected with small interfering RNA of BDNF were co-incubated with Müller cells to determine Müller cell proliferation and retrodifferentiation. β-catenin expression in the nucleus and GSK-3β phosphorylation were measured to determine the role of the Wnt pathway in Müller cells. The function of the retina in RCS rats was observed using flash electroretinogram.ResultsCo-incubation of ESCs with Müller cells or overexpression of BDNF contributed to Müller cell retrodifferentiation and proliferation, as evidenced by increased cell proliferation, fluorescence intensities of proliferation markers and retinal stem cell markers, and expression of BDNF and β-catenin, and suppressed GSK-3β phosphorylation. However, co-incubation with ESCs silencing BDNF or treatment with GW4869 inhibited the proliferation and retrodifferentiation of retinal Müller cells. In addition, exosome injection increased BDNF, BrdU, PH3, SOX2, and Pax6 expression, enhanced β-catenin expression in the nucleus, diminished GSK-3β, and improved retinal degeneration in RCS rats.ConclusionESC-Exos accelerated Müller cell retrodifferentiation and proliferation through Wnt pathway activation by delivering BDNF protein to Müller cells. |
| |
| Keywords: | Müller cell Embryonic stem cell BDNF Retrodifferentiation Retinal stem cell Wnt pathway |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
