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Gremlin-1 Is a Key Regulator of Endothelial-To-Mesenchymal Transition in Human Pulmonary Artery Endothelial Cells

Gremlin-1 Is a Key Regulator of Endothelial-To-Mesenchymal Transition in Human Pulmonary Artery Endothelial Cells

Yunxia Zhang, Meng Zhang, Wanmu Xie, Jun Wan, Xincao Tao, Min Liu, Yanan Zhen, Fan Lin, Bo Wu, Zhenguo Zhai, Chen Wang

Exp Cell Res. 2020 May 1;390(1):111941.

PMID: 32145252

Abstract:

Background:
Endothelial-to-mesenchymal transition (EndMT) has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). Gremlin-1 promotes vascular remodeling of PAH and mediates epithelial-mesenchymal transition, which is similar to EndMT. In the present study we investigated the potential role of gremlin-1 plays in EndMT of pulmonary artery endothelial cells (PAECs).
Methods:
Immunofluorescence staining was performed to detect the expression of alpha smooth muscle actin (α-SMA) and von Willebrand factor (VWF). Migration and angiogenic responses of PAECs were determined by transwell assay and tube formation assay, respectively. Protein expression levels were determined by western blotting.
Results:
Gremlin-1 induced EndMT of PAECs in a phospho-smad2/3-dependent manner. This was characterized by the loss of platelet endothelial cell adhesion molecule 1 and an increase in protein levels of a-SMA, nerve-cadherin, and matrix metalloproteinase 2. It was also determined that gremlin-1 facilitated the migration and angiogenic responses of PAECs in a dose-dependent manner. Bone morphogenetic protein 7 (BMP-7) was found to attenuate gremlin-1-mediated EndMT, migration and angiogenesis of PAECs by inducing phosphorylation of Smad1/5/8 and suppressing phosphorylation of Smad2/3.
Conclusion:
Gremlin-1 mediates EndMT in PAECs, and BMP-7 reverses gremlin-1-induced EndMT by an induction of p-Smad1/5/8 and suppression of p-Smad2/3.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413726	GREMLIN-1 human			Price

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