Silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway.

• 影响指数: 2.996
• 发表时间: May 2019
• 来源期刊: Kaohsiung J Med Sci
• DOI: 10.1002/kjm2.12034
• PMID: 30942529
• 文章类型: Journal Article
• 中科院分区: Q4
• 方向: 医学
• 作者列表: Chen JG,Fan HY,Wang T,Lin LY,Cai TG

关键词: ERK signaling pathway; KRT16; keratinocyte; psoriasis; vascular endothelial growth factor

Mesh: Adult; Aged; Case-Control Studies; Cell Proliferation; Female; Flavonoids / pharmacology; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; Keratin-16 / antagonists & inhibitors genetics metabolism; Keratinocytes / drug effects metabolism pathology; MAP Kinase Signaling System / genetics; Male; Middle Aged; Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors genetics metabolism; Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors genetics metabolism; Primary Cell Culture; Protein Kinase Inhibitors / pharmacology; Psoriasis / genetics metabolism pathology; RNA, Small Interfering / genetics metabolism; Vascular Endothelial Growth Factor A / antagonists & inhibitors genetics metabolism

Abstract

Psoriasis is a multisystem disease affecting about 2% of the population, while keratin16 (KRT16) has been reported to participate in psoriasis. However, the specific mechanism of KRT16 in psoriasis was inadequately investigated. The objective of the study was to elucidate the mechanism by which siRNA-mediated silencing of KRT16 affects keratinocyte proliferation and vascular endothelial growth factor (VEGF) secretion in psoriasis through the extracellular signal-related kinase (ERK) signaling pathway. Psoriasis-related core gene KRT16 was screened out. Then, the expression of KRT16, VEGF, and ERK signaling pathway-related genes was detected in psoriatic patients. To further investigate the mechanism of KRT16, keratinocytes in psoriatic patients were treated with KRT16 siRNA or/and ERK inhibitor (PD98059) to detect the changes in related gene expression and cell survival. KRT16 was involved in psoriasis development. The expression levels of KRT16, p-ERK1/2, and VEGF in lesion tissues are significantly elevated. Keratinocytes treated with KRT16-siRNA and KRT16-siRNA + PD98059 exhibited reduced KRT16, p-ERK1/2, and VEGF expression. The cell survival rate in cells treated with KRT16-siRNA, PD98059, and KRT16-siRNA + PD98059 reduced significantly. These findings indicate that silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway, which provides a basic theory in the treatment of psoriasis.