The Effects And Mechanism Of MiR-21 On Collagen Synthesis Of Huaman Keloids

Objective: Keloid is a clinical disease due to dermal injury characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition.The study found that in a variety of fibrotic diseases,the expression of miR-21 in myocardium,kidney,lung fibrosis was significantly increased and the miR-21 promotes the fibrosis.In our study,we found that the expression of miR-21 in keloid was significantly increased compared with that in normal skin.This paper mainly investigated the increased expression of miR-21 acted an important role in keloid formation.Methods: 1.Detection of the expression of miR-21,Smad7,Col1a1 and Col3a1 in normal skin and keloid fibroblasts by Real-time PCR.2.Transfection of miR-21 mimics and inhibitor,and detected the expression of Smad7,Col1a1 and Col3a1;detected cell proliferation with crystal violet staining.3.With exogenous TGF-β1,detected the miR-21 expression.The expression of Col1a1,Col3a1 and Smad7 was detected with the stimulation of TGF-β1,miR-21 analog or inhibitor.4.Smad 7 siRNA was transfected into fibroblast cells,and the expression of Col1a1,Col3a1 was detected.5.Explored the effect of miR-21 inhibitor on the growth of established nude mouse model of keloid in vivo.Results:1.the expression of miR-21,Col1A1,Col3A1 were higher in keloid tissue and its fibroblasts,while the expression of Smad7 was lower.2.With transfection of miR-21 mimic,mRNA and protein expression of Smad7 decreased,mRNA and protein expression of Col1A1,Col3A1 increased significantly.The proliferation ability of fibroblasts was significantly increased with transfection of miR-21 mimic.3.TGF-β1 induced the expression of miR-21,Col1A1,Col3A1 and decreased expression of Smad7;transfection of miR-21 mimic had the similar results,while transfection of miR-21 inhibitor had the opposite effect.4.Compared with the control group,normal fibroblast cells transfected with Smad 7 siRNA had the significantly increased the expression of Col1a1 and Col3a1.5The miR-21 inhibitor to reduce the volume and weight of keloid tissue in nude mice model.Conclusion: 1,The high expression miR-21 in keloid decreased the expression of Smad7,increased the expression of Col1A1,Col3A1;miR-21 can promote fibroblast proliferation ability.2,TGF-β1 promoted the expression of miR-21.TGF-β1 and miR-21 could promote the expression of Col1A1,Col3A1,and decreased the expression of Smad7.3,miR-21 inhibitor can significantly reduce the volume and weight of keloid in nude mice.