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.
Abbreviations:
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)Keywords
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Article info
Publication history
Published online: June 27, 2021
Accepted:
June 25,
2021
Received in revised form:
June 14,
2021
Received:
February 3,
2021
Identification
Copyright
© 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
