Role of TGF-β1/Smads Pathway in Regulation of Endothelial-Mesenchymal Transition in Hypoxia-Hypercapnia Pulmonary Hypertension

ZHANG Jingjing^1,2#, HUANG Danna^1#, WU Yuanling¹, GAO Hui¹, LOU Guoqiang¹, ZHOU Zhuolin¹, SHI Lingfang³, WANG Wantie¹*

(¹Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China; ²Department of Pathology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; ³Division of Pulmonary and Critical Care Medicine, Stanford University Medical School, Stanford CA94305-5236, USA)

Abstract:

This article aims to investigate the relationship between transforming growth factor β1 (TGFβ1)/Smads pathway and hypoxia-hypercapnia pulmonary hypertension and endoelial-mesenchymal transition (EndoMT). Rat pulmonary artery endothelial cells were identified by CD31 and α-SMA immunofluorescence double labeling. Cell viability was detected by CCK-8 assay. Cell migration was detected by Transwell chamber assay. mRNA and protein expression levels of CD31, α-SMA, TGF-β1 and Smad2/3 were detected by reverse transcription-PCR and Western blot, respectively. The results showed that the expression levels of α-SMA, TGF-β1 and Smad2/3 mRNA were up-regulated, and expression levels of α-SMA, TGF-β1 and p-Smad2/3 protein were upregulated, while the expression levels of CD31 mRNA and protein were down-regulated, and the cell viability was decreased while cell migration level was increased under hypoxia-hypercapnia environment. It also showed that the use of rhTGF-β1 promoted the above effects in a hypoxia-hypercapnia environment, whereas the use of SB-431542 reversed the effects of rhTGF-β1 in a hypoxia-hypercapnia environment. The results suggested that hypoxiahypercapnia can promote the occurrence of EndoMT in RPAECs. And inhibition of TGF-β1/Smads pathway can inhibit EndoMT and alleviate hypoxia-hypercapnia pulmonary hypertension.

CSTR: 32200.14.cjcb.2019.10.0012