Jafarinejad-Farsangi Saeideh, Farazmand Ali, Gharibdoost Farhad, Karimizadeh Elham, Noorbakhsh Farshid, Faridani Habibeh, Mahmoudi Mahdi, Jamshidi Ahmad Reza
Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran.
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int J Dermatol. 2016 Nov;55(11):1259-1267. doi: 10.1111/ijd.13308.
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.
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.
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.
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.
真皮成纤维细胞的长期激活是系统性硬化症（SSc）进行性纤维化的主要原因。SSc成纤维细胞中凋亡抑制似乎会使纤维化失调。微小RNA-21（miR-21）是一种促纤维化因子，在SSc皮肤和成纤维细胞的病变区域高表达。
采用实时聚合酶链反应和蛋白质印迹分析，评估miR-21对SSc患者真皮成纤维细胞中两个凋亡基因Bcl-2和Bax表达的影响。使用流式细胞术和Hoechst 33258染色试验检测凋亡细胞。
使用合成的miR-21 RNA过表达miR-21可增加SSc成纤维细胞中凋亡抑制因子Bcl-2的表达，并降低细胞命运决定因素Bax:Bcl-2的表达比率。对miR-21的反义抑制诱导了SSc成纤维细胞的高凋亡率。我们认为，这可能与Bcl-2表达降低以及Bax:Bcl-2比率的改变有关。
尽管需要进一步研究以确定潜在的凋亡途径，但我们认为抑制病变皮肤真皮成纤维细胞中的miR-21可能有助于控制SSc中的进行性纤维化。
