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Hyaluronan-CD44 Interaction Regulates Mouse Retinal Progenitor Cells Migration, Proliferation and Neuronal
Jian Ma1, Xiaoyun Fang2, Min Chen2
1Eye Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. jian_ma@zju.edu.cn.
Stem Cell Reviews and Reports
|September 14, 2023
Summary
Hyaluronan (HA)-CD44 interactions enhance retinal progenitor cell (RPC) adhesion and migration. This signaling pathway regulates RPC proliferation and differentiation, offering potential for vision-preserving cell therapies.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Cell Biology
Background:
- Cell-based therapies hold promise for replacing damaged retinal neurons and preserving vision.
- Retinal progenitor cell (RPC) migration, proliferation, and differentiation are crucial for successful retinal integration post-transplantation.
Purpose of the Study:
- To investigate the impact of Hyaluronan (HA)-CD44 interactions on RPC behavior.
- To elucidate the molecular mechanisms regulating RPC migration, proliferation, and differentiation mediated by HA-CD44 signaling.
Main Methods:
- Assessed CD44 expression in RPCs.
- Examined the effects of HA-CD44 interaction on RPC adhesion and migration.
- Investigated the roles of protein kinase C (PKC), Nanog, microRNA-21 (miR-21), Rho-Kinase (ROK), Grb2-associated binders (Gab-1), phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathways.
Main Results:
- HA-CD44 interaction significantly enhanced RPC adhesion and migration.
- HA-CD44 interaction stimulated miR-21 expression in a PKC/Nanog-dependent manner.
- PKC, Nanog, and miR-21 inhibition blocked HA-mediated RPC migration; ROK/Gab-1/PI3K/AKT signaling was essential for HA-CD44-induced proliferation and neuronal differentiation.
Conclusions:
- HA-CD44 signaling plays a critical role in regulating RPC migration, proliferation, and neuronal differentiation.
- This interaction pathway presents a novel strategy for controlling RPC fate.
- Findings provide insights for optimizing RPC-based therapeutic applications in retinal repair.
