A ROCK inhibitor suppresses the transforming growth factor-beta-2-induced endothelial–mesenchymal transition in Schlemm’s canal endothelial cells

• Published in: Scientific reports 2023-06, Vol.13 (1), p.9655-9655, Article 9655
• Main Authors: Fujimoto, Tomokazu, Inoue-Mochita, Miyuki, Inoue, Toshihiro
• Format: Article
• Language: English
• Subjects: 631/80; 692/699/3161; 692/699/3161/3169; Bone morphogenetic proteins; Cadherins; Canals (anatomy); Cell proliferation; Electrical resistivity; Endothelial Cells; Fibronectin; Glaucoma; Glaucoma, Open-Angle; Gremlin protein; Growth factors; Humanities and Social Sciences; Humans; Kinases; MAP kinase; mRNA; multidisciplinary; N-Cadherin; Phosphorylation; rho-Associated Kinases; Rocks; Schlemm's Canal; Science; Science (multidisciplinary); Transforming Growth Factor beta2 - pharmacology; Transforming growth factor-b1; Transforming Growth Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-36808-8

In the normal eye, most of the aqueous humor drains through the trabecular meshwork (TM) and Schlemm’s canal (SC). The concentration of transforming growth factor beta 2 (TGF-β2) is increased in the aqueous humor of primary open angle glaucoma patients. TGF-β2 increases outflow resistance by affecting the TM and SC, and endothelial–mesenchymal transition (EndMT) of SC cells is involved in these changes. Here, we investigated the effect of a ROCK inhibitor on TGF-β2-induced EndMT in SC cells. The ROCK inhibitor Y-27632 suppressed the TGF-β2-induced increase in the trans-endothelial electrical resistance (TER) and proliferation of SC cells. Y-27632 suppressed the expression of α-SMA, N-cadherin, and Snail, which are upregulated by TGF-β2. Moreover, TGF-β2 decreased mRNA levels of bone morphogenetic protein (BMP) 4 and increased those of the BMP antagonist gremlin (GREM1), but Y-27632 significantly suppressed these changes. Y-27632 also inhibited TGF-β2-induced phosphorylation of p-38 mitogen-activated protein kinase (MAPK). BMP4 and the p-38 MAPK inhibitor SB203580 suppressed the TGF-β2-induced TER elevation in SC cells. Moreover, SB203580 suppressed TGF-β2-induced upregulation of fibronectin, Snail, and GREM1. These results indicate that a ROCK inhibitor inhibited the TGF-β2-induced EndMT in SC cells, implying the involvement of p38 MAPK and BMP4 signaling.