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

Yongjian Li,Juan Su,Guiying Zhang,Fangfang Li,Xiang Chen,Nicola Amodio

doi:10.1371/journal.pone.0175459

Abstract

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-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA). In addition, we found that HIF-1α 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-1α and VEGFA in psoriasis for the first time, and provide diagnostic markers and a novel target for psoriasis treatment.

Highlights

Psoriasis is a common chronic inflammatory disease of skin affecting 2 to 3% of the world population
Lower miR-150 expression in psoriasis was significantly correlated with a longer disease duration (P = 0.011), worse Psoriasis Area and Severity Index (PASI) (P = 0.019) and larger body surface area (BSA) (P = 0.014) (Table 2)
During the psoriasis process, proliferating keratinocytes exhibit hypoxia-induced vascular endothelial growth factor A (VEGFA) expression, which initiates a process that aims to achieve the proper flow of blood through the lesional skin [28, 29]

Summary

Introduction

Psoriasis is a common chronic inflammatory disease of skin affecting 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 [7, 8]. MiR-150 regulates keratinocytes proliferation via targeting HIF-1a and VEGFA likely that exaggerated keratinocytes proliferation is closely related to disease expression. Keratinocytes may be crucial in initiating, sustaining, and amplifying the inflammatory responses by expressing molecules involved in T-cell recruitment, retention, and activation [9]. Recent research demonstrated that there were various factors participated in pathological progress of psoriasis, such as hypoxia [10,11,12]

Methods

Results

Conclusion