Lei R, Shen J, Zhang S, Liu A, Chen X, Wang Y, Sun J, Dai S, Xu J

Keloids are a common type of pathological skin healing, characterized by the destruction of the vascular network. Thus, keloids often exhibit anoxic conditions. Hypoxia-inducible factor-1? (HIF-1?) is a core factor that mediates hypoxia stress responses and allows the cells to adapt to low-oxygen conditions. In the current study, we identified ...

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that Parkin acted as an E3 ubiquitin ligase, contributing to the degradation of HIF-1? in keloid fibroblasts (KFs). Silencing of Parkin in KFs upregulated HIF-1? expression and prolonged its protein half-life. Furthermore, Parkin influenced transforming growth factor ? (TGF-?)/Smad signaling by targeting HIF-1?. Under hypoxic conditions, silencing Parkin enhanced KF proliferation and inhibited apoptosis through the TGF-?/Smad signaling pathway. Notably, metformin, an antidiabetic drug, could significantly induce Parkin expression and enhance the interaction between Parkin and HIF-1?. As a result, we revealed an important mechanism for Parkin in keloid development and suggested that targeting Parkin could be an alternative method for keloid treatment.

Date: Feb. 19, 2019

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