rhBMP‑7 suppresses TGF‑β1‑induced endothelial to mesenchymal transition in circulating endothelial cells by regulating Smad5

Ge,Weili; Mi,Yafei; Xu,Shasha; Li,Tao; Lu,Yifei; Jiang,Jianjun

doi:10.3892/mmr.2019.10842

rhBMP‑7 suppresses TGF‑β1‑induced endothelial to mesenchymal transition in circulating endothelial cells by regulating Smad5

Authors:
- Weili Ge
- Yafei Mi
- Shasha Xu
- Tao Li
- Yifei Lu
- Jianjun Jiang
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Affiliations: Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, Zhejiang 317000, P.R. China
Published online on: November 21, 2019 https://doi.org/10.3892/mmr.2019.10842
Pages: 478-484

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Abstract

Endothelial to mesenchymal transition (EndMT) has been confirmed to participate in several cardiovascular diseases. In addition, EndMT of circulating endothelial cells (CECs) contributes to the pathology of musculoskeletal injury. However, little is known about the molecular mechanism of CECs undergoing EndMT. In the present study, human CECs were isolated and identified using anti‑CD146‑coupled magnetic beads. CECs were exposed to transforming growth factor (TGF)‑β1 or TGF‑β1 + recombinant human bone morphogenetic protein 7 (rhBMP‑7) or TGF‑β1 + rhBMP‑7 + Smad5 antagonist Jun activation domain‑binding protein 1. Vascular endothelial (VE)‑cadherin and vimentin expression were detected by immunofluorescence staining in TGF‑β1‑treated CECs. The expression levels of von Willebrand factor (vWF), E‑selectin, VE‑cadherin, vimentin, fibronectin, α smooth muscle actin (α‑SMA) and Smad2/3 were detected by reverse transcription‑quantitative PCR or western blot analysis. It was identified that rhBMP‑7 attenuated TGF‑β1‑induced endothelial cell injury. TGF‑β1 could induce the EndMT process in CECs, as confirmed by the co‑expression of VE‑cadherin and vimentin. TGF‑β1 significantly reduced the expression of VE‑cadherin, and induced the expression of vimentin, fibronectin and α‑SMA. rhBMP‑7 reversed the effects of TGF‑β1 on the expression of these genes. Additionally, Smad5 antagonist reversed the effects of rhBMP‑7 on TGF‑β1‑induced EndMT, and upregulated rhBMP‑7‑inhibited Smad2/3 expression. In conclusion, TGF‑β1 could induce EndMT in CECs and rhBMP‑7 may suppress this process by regulating Smad5.

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