ITE promotes hypoxia‐induced transdifferentiation of human pulmonary arterial endothelial cells possibly by activating transforming growth factor‐β/Smads and MAPK/ERK pathways. Issue 12 (11th July 2019)

• Record Type: Journal Article
• Authors: Wang, Jinxia; Yan, Guosen; Guo, Haixu; Zhu, Ying; Shui, Xiaorong; He, Yuan; Chen, Can; Lei, Wei
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 12(2019)
• Page Start: 19567
• Page End: 19577
• Publication Date: 2019-07-11
• Subjects: endothelial cells -- hypoxia -- ITE -- pulmonary vascular remodeling -- smooth muscle‐like cells; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29264
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: This study aimed to investigate the transdifferentiation of human pulmonary arterial endothelial cells (HPAECs) into smooth muscle like (SM‐like) cells under hypoxic conditions and reveal the role of endogenous small molecular compound 2‐(1′ H ‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylicacid methyl ester (ITE) in this process. HPAECs were treated by hypoxia and hypoxia + ITE with different durations. The endothelial markers (CD31 and VE‐cad) and smooth muscle markers (α‐SMA, SM22α, and OPN) were investigated by immunofluorescence double staining, and their expressions, along with the differentiation regulators transforming growth factor‐β (TGF‐β) ligands and downstream signals including TGF‐β1, bone morphogenetic protein (BMP2), BMP9, Samd2/3, ERK, and p38 MAPK, were determined by Western blot analysis. The viability and proliferation of HPAECs were detected by Cell Counting Kit‐8 (CCK‐8) method and bromodeoxyuridine (BrdU) assays. As a result, hypoxia induced HPAECs transdifferentiation from paving‐stone‐like into polygonal or spindle cells, whose number increased greatly after additional ITE stimulation for 7 days. Compared with the normoxic HPAECs, the expression of endothelial markers reduced and smooth muscle markers were enhanced with the extension of hypoxia + ITE treatment, and meanwhile the cell viability increased significantly. Hypoxia could promote expression of TGF‐β1 protein rather than BMP2 and BMP9, and regulate phosphorylation levels of Samd2/3, ERK and p38 MAPK in different manners. In conclusion, ITE can promote the hypoxia‐induced transdifferentiation of HPAECs into SM‐like cells via TGF‐β/Smads and MAPK/ERK pathways. Abstract : This study supported the promising pathway that SM‐like cells could originate from human pulmonary arterial endothelial cells (HPAECs) induced by hypoxia in vitro, and the endogenous small molecule compound 1′ H ‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylicacid methyl ester (ITE) promoted effectively hypoxia‐induced transdifferentiation of HPAECs by activating transforming growth factor‐β/Smads and MAPK/ERK signal pathways.