MicroRNA-30c attenuates fibrosis progression and vascular dysfunction in systemic sclerosis model mice.

Yosuke Kanno,Kei-Ichi Ozaki,Hirofumi Niwa,Mariko Seishima,En Shu

doi:10.1007/s11033-021-06368-z

Yosuke Kanno, Kei-Ichi Ozaki + Show 3 more

Open Access

https://doi.org/10.1007/s11033-021-06368-z

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Abstract

Systemic sclerosis (SSc) is characterized by peripheral circulatory disturbance and fibrosis in skin and visceral organs. We recently demonstrated that α2-antiplasmin (α2AP) is elevated in SSc dermal fibroblasts and SSc model mice, and is associated with fibrosis progression and vascular dysfunction. In the present study, we predicted that α2AP could be a target of microRNA-30c (miR-30c) using TargetScan online database, and investigated the effect of miR-30c on the pathogenesis of SSc using a bleomycin-induced SSc model mice. miR-30c attenuated α2AP expression, and prevented the pro-fibrotic changes (increased dermal thickness, collagen deposition, myofibroblast accmulation) and the vascular dysfunction (the reduction of vascular endothelial cells (ECs) and blood flow) in the skin of SSc model mice. Furthermore, miR-30c suppressed pulmonary fibrosis progression in the SSc model mice. miR-30c exerts the anti-fibrotic and anti-angiopathy effects on SSc model mice, and might provide a basis for clinical strategies for SSc.

Highlights

Systemic sclerosis (SSc) is characterized by the fibrosis of skin and visceral organs, and peripheral circulatory disturbance [1]
It has been reported that the level of PAP in plasma is elevated in SSc patients [13] and the expression of α2AP is elevated in the serum and skin of SSc model mice and SSc dermal fibroblasts [14,15,16], and the blockade of α2AP prevents pro-fibrotic changes and vascular damage in SSc model mice, and reversed a pro-fibrotic phenotype of SSc dermal fibroblasts [12, 15, 17]
We showed the expression of α2AP is elevated in the serum and skin of SSc model mice and SSc dermal fibroblasts [14,15,16], and the increased in α2AP expression affects vascular dysfunction and fibrosis progression in SSc model mice and SSc dermal fibroblasts [15, 17, 19]

Summary

Introduction

Systemic sclerosis (SSc) is characterized by the fibrosis of skin and visceral organs, and peripheral circulatory disturbance [1]. Vascular damage, such as the reduction of blood vessels and blood flow, occurs in the early stages of the disease, and is associated with fibrosis progression [2]. This process usually occurs over many months and years, and can lead to organ dysfunction or death. Alpha2-antiplasmin (α2AP; SERPINF2) is the principal inhibitor of plasmin and inhibits the fibrinolysis [3, 4]. The changes in α2AP expression may contribute to fibrosis progression in SSc

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