Inhibition of MicroRNA-21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis.

Abstract:

BACKGROUND:Prolonged activation of dermal fibroblasts is the main cause of progressive fibrosis in systemic sclerosis (SSc). It seems that inhibition of apoptosis in SSc fibroblasts deregulates fibrosis. MicroRNA-21 (miR-21) is a pro-fibrotic factor with high expression in lesional areas of SSc skin and fibroblasts. METHODS:The effects of miR-21 on expression of Bcl-2 and Bax, two apoptotic genes, in dermal fibroblasts of SSc patients were evaluated using real-time polymerase chain reaction and Western blot analysis. Apoptotic cells were detected using flow cytometry and Hoechst 33258 staining assays. RESULTS:Overexpression of miR-21 using synthetic miR-21 RNA increased expression of Bcl-2, an inhibitor of apoptosis, and decreased the Bax : Bcl-2 expression ratio, a cell fate determinant, in SSc fibroblasts. Antisense inhibition of miR-21 induced a high rate of apoptosis in SSc fibroblasts. We propose that this may be associated with a decrease in Bcl-2 expression and a shift in the Bax : Bcl-2 ratio. CONCLUSIONS:Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR-21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.

journal_name

Int J Dermatol

authors

Jafarinejad-Farsangi S,Farazmand A,Gharibdoost F,Karimizadeh E,Noorbakhsh F,Faridani H,Mahmoudi M,Jamshidi AR

doi

10.1111/ijd.13308

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

1259-1267

issue

11

eissn

0011-9059

issn

1365-4632

journal_volume

55

pub_type

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