医学
瘢痕疙瘩
同源盒
发病机制
纤维化
蛋白激酶A
癌症研究
病理
激酶
细胞生物学
遗传学
基因
转录因子
生物
作者
Yixuan Zhao,Guoyou Zhang,Anyuan Wang,Yahong Chen,Damu Lin,Qingfeng Li
出处
期刊:Annals of Plastic Surgery
[Ovid Technologies (Wolters Kluwer)]
日期:2017-12-01
卷期号:79 (6): 546-551
被引量:10
标识
DOI:10.1097/sap.0000000000001243
摘要
Epithelial-mesenchymal transition (EMT) plays a critical role in fibrotic keloid formation, which is characterized by excessive collagen and extracellular matrix synthesis and deposition. Growing evidence suggests that the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) acts upstream of several major fibrosis signaling pathways; however, the role of HIPK2 in the keloid fibrogenesis remains unknown. In the current study, we investigated the roles of HIPK2 in the pathogenesis of keloids. Primary normal skin and keloid keratinocytes were cultured and pretreated with transforming growth factor (TGF)-β1. Next, keratinocytes were transfected with scrambled small interfering RNA (siRNA) and anti-HIPK2 siRNA. The TGF-β1-associated HIPK2 alterations were investigated by quantitative real-time polymerase chain reaction. Protein levels were analyzed by western blotting. The HIPK2 was markedly increased in the keloid-derived keratinocytes compared with normal skin keratinocytes. In addition, HIPK2 induced the expression of EMT markers in normal skin keratinocytes by TGF-β1-SMAD family member 3 (SMAD3). The effect of TGF-β1-related EMT markers and SMAD3 phosphorylation in response to added TGF-β1 was significantly abrogated when the cells were transfected with HIPK2 siRNA. We conclude that HIPK2 is a crucial factor in the pathogenesis of keloids, suggesting that HIPK2 might be a novel potential drug target for antikeloid therapy.
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