GSK-3 inhibition reverts mesenchymal transition in primary human corneal endothelial cells

• DOI: 10.1016/j.ejcb.2023.151302
• Publication Date: 2023-03-07T21:28:45Z
• Authors: Eleonora Maurizi; Alessia Merra; Claudio Macaluso; Davide Schiroli; Graziella Pellegrini
• Keywords: Corneal Endothelium

Human corneal endothelial cells are organized in a tight mosaic of hexagonal and serve critical function maintaining hydration clear vision. Regeneration the tissue is hampered by its poor proliferative capacity, which partially retrieved vitro, albeit only for limited number passages before undergo mesenchymal transition (EnMT). Although different culture conditions have been proposed order to delay this process prolong cell passages, EnMT has still not fully understood successfully counteracted. In perspective, we identified herein single GSK-3 inhibitor, CHIR99021, able revert avoid primary human (HCEnCs) from old donors until late vitro (P8), as shown morphology analysis (circularity). accordance, CHIR99021 reduced expression α-SMA, an marker, while restored markers such ZO-1, Na+/K+ ATPase N-cadherin, without increasing proliferation. A further on RNA confirmed that induced downregulation (α-SMA CD44), upregulation proliferation repressor p21 revealed novel insights into β-catenin TGFβ pathways intersections HCEnCs. The use sheds light mechanisms involved EnMT, providing substantial advantage HCEnCs preserving correct phenotype. Altogether, these results bring crucial advancements towards improvement based therapy.