Hyaluronan-CD44 Interaction Regulates Mouse Retinal Progenitor Cells Migration, Proliferation and Neuronal Differentiation
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Published:2023-09-14
Issue:8
Volume:19
Page:2929-2942
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ISSN:2629-3269
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Container-title:Stem Cell Reviews and Reports
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language:en
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Short-container-title:Stem Cell Rev and Rep
Author:
Ma JianORCID, Fang Xiaoyun, Chen Min, Wang Yao, Zhang Li
Abstract
AbstractCell-based therapies have shown great potential because of their abilities to replace dying retinal neuron cells and preserve vision. The migration, proliferation and differentiation of retinal progenitor cells(RPCs) plays a vital role in the integration of the RPCs into the retina when transplanted into the host. Our study aimed to explore the effects of Hyaluronan(HA)-CD44 interactions on the regulation of RPCs migration, proliferation and differentiation, and investigate the underlying regulatory mechanisms. We found that CD44 was expressed in RPCs, and the HA-CD44 interaction markedly improved RPCs adhesion and migration. The stimulation of microRNA-21(miR-21) expression by the HA-CD44 interaction was protein kinase C (PKC)/Nanog-dependent in RPCs. Treatment of RPCs with PKC- or Nanog-specific ASODN or miR-21 antagomir effectively blocked HA-mediated RPCs adhesion and migration. Moreover, Rho-Kinase(ROK)/ Grb2-associated binders(Gab-1) associated phosphatidylinositol 3-kinase(PI3K)/AKT signalling activation was required for HA-CD44 interaction mediated RPCs proliferation and neuronal differentiation. Our findings demonstrated new roles for the HA-CD44 interaction in regulating the migration, proliferation and neuronal differentiation of RPCs. HA-CD44 signalling could represent a novel approach to controlling RPC fates, and the findings may be instructive for the application of RPCs for future therapeutic applications.
Graphical Abstract
Funder
Natural Science Foundation of Jilin Province Natural Science Foundation of Zhejiang Province
Publisher
Springer Science and Business Media LLC
Reference32 articles.
1. Mandeep, S., Singh, S. S., Park, T. A., Albini, M., Valeria Canto-Soler, H., Klassen, R. E., MacLaren, M., Takahashi, A., Nagiel, S. D., & Schwartz, Kapil Bharti. (2020) retinal stem cell transplantation: Balancing Safety and potential. Progress in Retinal and Eye Research 75, 100779. 2. Jones, M. K., Lu, B., Girman, S., & Wang, S. (2017). Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases. Progress in Retinal and Eye Research, 58, 1–27. 3. Nazari, H., Zhang, L., Zhu, D., Chader, G. J., Falabella, P., Stefanini, F., Rowland, T., Clegg, D. O., Kashani, A. H., Hinton, D. R., & Humayun, M. S. (2015). Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Progress in Retinal and Eye Research, 48, 1–39. 4. Chichagova, V., Hallam, D., Collin, J., Zerti, D., Dorgau, B., Felemban, M., & Lako, M., David H. Steel. (2018)Cellular regeneration strategies for macular degeneration: Past, present and future. Eye (London, England) 32(5): 946–971. 5. Klassen, H. J., Ng, T. F., Kurimoto, Y., Kirov, I., Shatos, M., Coffey, P., & Young, M. J. (2004). Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior. Invest Ophthalmol Vis Sci, 45, 4167–4173.
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