Oxidative stress induced overexpression of miR 25: the mechanism underlying the degeneration of melanocytes in vitiligo
Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR 25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR 25 promoted the H2O2 induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR 25 caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR 25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR 25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR 25. Taken together, our study demonstrates that oxidative stress induced overexpression of miR 25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR 25 as a potential drug target for anti oxidative therapy in vitiligo.
Cell Death and Differentiation