Bone morphogenetic protein-7 inhibits endothelial-to-mesenchymal transition in primary human umbilical vein endothelial cells and mouse model of systemic sclerosis via Akt/mTOR/p70S6K pathway. Issue 2 (August 2021)

• Record Type: Journal Article
• Authors: Shen, Chen; Jiang, Ying; Li, Qiao; Liu, Chaofan; Hu, Feifei; Li, Ming
• Is Part Of: Journal of dermatological science. Volume 103:Issue 2(2021)
• Page Start: 82
• Page End: 92
• Publication Date: 2021-08
• Subjects: SSc systemic sclerosis -- EndoMT endothelial-to-mesenchymal transition -- BMP-7 bone morphogenic protein-7 -- TGF-β transforming growth factor beta -- HUVECs human umbilical vein endothelial cells -- ECs endothelial cells -- BLM bleomycin -- VE-cad vascular endothelial-cadherin -- α-SMA α-smooth muscle actin; Endothelial-to-mesenchymal transition -- Endothelial cells -- Bone morphogenic protein-7 -- Transforming growth factor beta -- Systemic sclerosis; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2021.06.009
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: The mechanism of SSc involves vascular disorder, inflammation and tissue fibrosis. EndoMT may play vital role in the pathogenesis of vascular remodeling in SSc. BMP-7 inhibits EndoMT through Akt/mTOR/p70S6K signaling pathway in vitro and in vivo. Abstract: Background: Systemic sclerosis (SSc) is an autoimmune inflammatory and vascular disorder that causes tissue fibrosis of the skin and internal organs. Endothelial-to-mesenchymal transition (EndoMT) has been considered an important mechanism in the pathogenesis of vascular remodeling in SSc. Recent studies suggested that bone morphogenic protein 7 (BMP-7) has anti-fibrotic effects in several fibrotic diseases. Objectives: To investigate the mechanism of BMP-7 in inhibiting TGF-β-induced EndoMT in systemic sclerosis (SSc). Methods: Skin tissues of both healthy controls and SSc patients were detected the distribution of BMP-7. TGF-β was applied to induce the EndoMT model of human umbilical vein endothelial cells (HUVECs), and bleomycin was used to established the SSc mouse model. After treatment of BMP-7, the protein levels of endothelial specific markers, mesenchymal cell products, transcription factors and Akt signal pathway were examined by western blotting, immunofluorescence or immunohistochemistry both in vivo and in vitro. Results: The expression of BMP-7 was decreased in the basal layer of epidermis and dermis of SSc patients. EndoMT in TGF-β-treated HUVECs and skins of SSc mouse model were markedly attenuated after treatment with rh-BMP-7. Moreover, Akt/mTOR/p70S6K phosphorylation was involved in EndoMT and BMP-7 suppressed TGF-β- or bleomycin-induced theses phosphorylation in HUVECs or SSc mouse model. Conclusion: BMP-7 reduced the production of TGF-β-induced EndoMT in HUVECs and SSc mouse model through Akt/mTOR/p70S6K signaling pathway. These findings suggested that BMP-7 could be employed as a promising antifibrotic therapy for SSc.