Curcumol suppresses endothelial-to-mesenchymal transition via inhibiting the AKT/GSK3β signaling pathway and alleviates pulmonary arterial hypertension in rats

Nie, Xinran; Wu, Zhuhua; Shang, Jin; Zhu, Li; Liu, Yingli; Qi, Yong

doi:10.1016/j.ejphar.2023.175546

Cited by 4 publications

(1 citation statement)

References 51 publications

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“…In this study, although there was no statistically significant difference, Y-27632 showed a tendency to suppress the phosphorylation of Akt and Smad3 by TGF-β2. It has been reported in other endothelial cells that suppression of Akt 42 , 43 and Smad 44 – 46 signals suppress EndMT. In addition, we previously reported that HDAC inhibitors significantly suppressed Akt signaling and suppressed EndMT in SC cells 17 .…”

Section: Discussionmentioning

confidence: 89%

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

Fujimoto

Inoue-Mochita

Inoue

2023

Sci Rep

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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.

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