MiR-150 regulates human keratinocyte proliferation in hypoxic conditions through targeting HIF-1α and VEGFA: Implications for psoriasis treatment

被引:51
作者
Li, Yongjian [1 ]
Su, Juan [2 ]
Li, Fangfang [2 ]
Chen, Xiang [3 ]
Zhang, Guiying [4 ]
机构
[1] Nanhua Univ, Affiliated Hosp 2, Dept Dermatol, Hengyang, Hunan, Peoples R China
[2] Cent S Univ, XiangYa Hosp, Dept Dermatol, Hunan Key Lab Skin Canc & Psoriasis, Changsha, Hunan, Peoples R China
[3] Cent S Univ, XiangYa Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China
[4] Cent S Univ, Xiangya Hosp 2, Dept Dermatol, Changsha, Hunan, Peoples R China
关键词
ENDOTHELIAL GROWTH-FACTOR; OVER-EXPRESSION; UP-REGULATION; MICRORNAS; ANGIOGENESIS; SKIN; INFLAMMATION; RNAS;
D O I
10.1371/journal.pone.0175459
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Psoriasis is a common and chronic autoimmune skin disease which affects 2 to 3% of the world population. Abnormal proliferation of human keratinocytes is an important feature of psoriasis, along with local hypoxia and vascular abnormal growth. To leverage recent molecular findings into the personalized treatment of psoriasis, we need a strategy that integrates clinical stratification with molecular phenotyping. MicroRNAs (miRNAs) are a large family of small non-coding RNA which regulates diverse biological process, including cell proliferation, by modulating gene expression at the posttranscriptional level. In the present study, we indicated that miR-150 specifically down-regulated expressed in psoriatic skin lesions, and could inhibit HaCaT cells and primary adult human keratinocytes (HKCs)' proliferation in either normal or hypoxia conditions; by direct targeting, miR-150 could also regulate the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor A (VEGFA). In addition, we found that HIF-1 alpha and VEGFA were highly expressed in the lesional psoriatic skin compared with the non-lesional psoriatic skin, and negatively correlated with miR-150 expression. Taken together, we indicated miR-150 regulates human keratinocytes' proliferation in hypoxic conditions through targeting HIF-1 alpha and VEGFA in psoriasis for the first time, and provide diagnostic markers and a novel target for psoriasis treatment.
引用
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页数:15
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