Mechanism of miR-125a-3p targeting FOXM1 in regulating skin injury and inflammatory response in psoriasis rats
10.3969/j.issn.1000-484X.2024.12.012
- VernacularTitle:miR-125a-3p靶向FOXM1调控银屑病大鼠皮肤损伤和炎症反应的作用机制
- Author:
Zhao JIN
1
;
Zhong LIU
;
Jing PENG
;
Rongyi HU
;
Juan WU
;
Qinsi HUANG
;
Fei WANG
Author Information
1. 武汉市第一医院皮肤科,武汉 430022
- Keywords:
miR-125a-3p;
Forkhead box protein M1;
Psoriasis;
Skin injury;
Inflammatory response;
Keratinocytes
- From:
Chinese Journal of Immunology
2024;40(12):2531-2536,2542
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore effect of miR-125a-3p on skin injury and inflammatory response in psoriasis rats and its mechanism.Methods:SD rats were randomly divided into control group,psoriasis group,miR-NC group and miR-125a-3p group.Psoriasis Area and Severity Index(PASI)score and Baker score were measured on rats;levels of IL-6,IL-1β and TNF-α in rat skin tissue were detected by ELISA;qRT-PCR was used to detect miR-125a-3p expression;mRNA and protein expressions of forkhead box protein M1(FOXM1)in rat skin tissue were detected by qRT-PCR and Western blot.Keratinocytes from psoriasis rats were isolated and cultured,targeting relationship between miR-125a-3p and FOXM1 was verified by dual-luciferase reporter gene assay.Inhibiting or overexpressing miR-125a-3p and FOXM1 was overexpressed on basis of overexpressing miR-125a-3p,respectively.miR-125a-3p,FOXM1 mRNA and protein expressions in cells and IL-6,IL-1β,TNF-α levels in cell culture supernatants were detected,CCK-8 method was applied to detect cell viability,and flow cytometry was used to detect apoptosis rate.Results:Compared with control group,miR-125a-3p expression in skin tissue of rats in psoriasis group was decreased,PASI score,Baker score,IL-6,IL-1β,TNF-α levels,and FOXM1 mRNA and protein expressions were increased(P<0.05);compared with psoriasis group and miR-NC group,expression of miR-125a-3p in skin tissue of rats in miR-125a-3p group was increased,PASI score,Baker score,IL-6,IL-1β,TNF-α levels,and expressions of FOXM1 mRNA and protein were decreased(P<0.05).There was a targeting relationship between miR-125a-3p and FOXM1.After inhibiting miR-125a-3p expression,FOXM1 mRNA and protein expressions in cells,cell viability and IL-6,IL-1β,TNF-α levels in cell culture supernatant were increased,and apoptosis rate was decreased(P<0.05),while overexpression of miR-125a-3p had opposite effect.Overexpression of FOXM1 attenuated effects of overexpression of miR-125a-3p on cell viability,apopto-sis rate and inflammatory response.Conclusion:miR-125a-3p is lowly expressed in skin lesions of psoriasis rats,whose overexpression may inhibit proliferation of keratinocytes and promote apoptosis by targeting FOXM1,improve skin injury and reduce inflammatory response in psoriasis rats.