Inhibition of Microrna-21 Induces Apoptosis in Dermal Fibroblasts of Patients With Systemic Sclerosis Publisher Pubmed



Jafarinejadfarsangi S¹ ; Farazmand A¹ ; Gharibdoost F² ; Karimizadeh E¹ ; Noorbakhsh F³ ; Faridani H² ; Mahmoudi M² ; Jamshidi AR² Show Affiliations
Source: International Journal of Dermatology Published:2016

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. © 2016 The International Society of Dermatology