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Inactivating the ubiquitin ligase Parkin suppresses cell proliferation and induces apoptosis in human keloids
Author(s) -
Lei Rui,
Shen Jian,
Zhang Shizhen,
Liu Aiyu,
Chen Xi,
Wang Yang,
Sun Jiaqi,
Dai Siya,
Xu Jinghong
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28332
Subject(s) - parkin , ubiquitin ligase , ubiquitin , gene silencing , keloid , downregulation and upregulation , apoptosis , microbiology and biotechnology , cancer research , smad , signal transduction , chemistry , hypoxia (environmental) , autophagy , biology , medicine , biochemistry , pathology , disease , organic chemistry , oxygen , parkinson's disease , gene
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‐1α (HIF‐1α) 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 that Parkin acted as an E3 ubiquitin ligase, contributing to the degradation of HIF‐1α in keloid fibroblasts (KFs). Silencing of Parkin in KFs upregulated HIF‐1α expression and prolonged its protein half‐life. Furthermore, Parkin influenced transforming growth factor β (TGF‐β)/Smad signaling by targeting HIF‐1α. Under hypoxic conditions, silencing Parkin enhanced KF proliferation and inhibited apoptosis through the TGF‐β/Smad signaling pathway. Notably, metformin, an antidiabetic drug, could significantly induce Parkin expression and enhance the interaction between Parkin and HIF‐1α. 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.