In:
Biochemistry and Cell Biology, Canadian Science Publishing, Vol. 96, No. 5 ( 2018-10), p. 548-555
Abstract:
MicroRNA-21 (miR-21) has been found to be upregulated in keloid tissue and to affect the proliferation and apoptosis of keloid fibroblasts; however, the possible mechanisms remain unclear. In this study, we aimed to evaluate the role of miR-21 in FasL-induced caspase-8 activation and the mitochondria-mediated apoptotic signaling pathway in keloid fibroblasts. Our study found that the protein level of FasL was decreased by miR-21 over-expression, while being enhanced by miR-21 inhibition in keloid fibroblasts. Subsequently, the mitochondria-mediated apoptosis of keloid fibroblasts was restrained by miR-21 over-expression, as evidenced by enhanced mitochondrial membrane potential and decreased production of mitochondrial ROS. Moreover, over-expression of miR-21 inhibited the activation of the caspase-8 and the mitochondria-mediated apoptotic signaling pathway. As expected, inhibition of miR-21 had the opposite effects. Finally, silencing of FasL suppressed miR-21 inhibition-induced apoptosis by inactivation of caspase-8 and the mitochondria-mediated apoptotic signaling pathway, which was comparable to Z-IETD-FMK, a caspase-8 inhibitor. Taken together, these results suggest that miR-21 regulates the apoptosis of keloid fibroblasts via targeting FasL, and caspase-8 and the mitochondria-mediated apoptotic signaling pathway is involved in this process. Our findings provide evidence that miR-21 may be considered to be a therapeutic target for keloids.
Type of Medium:
Online Resource
ISSN:
0829-8211
,
1208-6002
DOI:
10.1139/bcb-2017-0306
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2018
SSG:
12
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