ITE promotes hypoxia‐induced transdifferentiation of human pulmonary arterial endothelial cells possibly by activating transforming growth factor‐β/Smads and MAPK/ERK pathways
Autor: | Yuan He, Wei Lei, Can Chen, Jinxia Wang, Guosen Yan, Xiaorong Shui, Ying Zhu, Haixu Guo |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway CD31 Indoles MAP Kinase Signaling System p38 mitogen-activated protein kinases Myocytes Smooth Muscle Smad Proteins Pulmonary Artery Bone morphogenetic protein p38 Mitogen-Activated Protein Kinases Biochemistry Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine medicine Humans Viability assay Hypoxia Molecular Biology Cells Cultured Cell Proliferation Chemistry Transdifferentiation Endothelial Cells Cell Biology Hypoxia (medical) Cell biology Thiazoles 030104 developmental biology 030220 oncology & carcinogenesis Cell Transdifferentiation medicine.symptom Signal Transduction Transforming growth factor |
Zdroj: | Journal of Cellular Biochemistry. 120:19567-19577 |
ISSN: | 1097-4644 0730-2312 |
Popis: | 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. |
Databáze: | OpenAIRE |
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