Study on the role of activation of TGF-β pathway by ASPN in the occurrence and develop-ment of keloid and the underlying mechanisms
XU Xueyan
CHEN Junyi
YAO Liuyi
DENG Chengcheng
Abstract:Objective To investigate the role of ASPN in the development of keloid and the underlying mechanisms.Methods Immunofluorescence staining was used to assess the expres-sion levels of ASPN in keloid of keloid patients and normal scar.WB and qRT-PCR were used to assess the activity of TGF-β pathway and expression levels of α-SMA、Collagen Ⅰ/Ⅲ,COMP and POSTN in fibroblasts with overexpression of ASPN,ASPN-treated fibroblasts and Keloid fibroblasts with ASPN knockdown.Moreover,wound healing was observed in C57BL/6J mice treated with or without ASPN at 0 d,3 d,7 d,and 14 d after wound.The expression levels of α-SMA、CollagenⅠ/Ⅲ and TGF-β in the wounded skin were assessed by immunofluorescence staining 14 days af-ter wound.Results ASPN was highly expressed in keloid fibroblasts.The expression levels of α-SMA、Collagen Ⅰ/Ⅲ、COMP and POSTN were significantly increased,and the TGF-β signaling pathway was activated in fibroblasts after either overexpression of or stimulation with ASPN(P<0.05).In contrast,knockdown of ASPN significantly decreased the expression levels of α-SMA、Collagen Ⅰ/Ⅲ,COMP and POSTN and inhibited TGF-β3 pathway in fibroblasts from keloids(P<0.05).In addition,ASPN significantly increased the expression levels of p-SMAD2、α-SMA and Collagen Ⅰ and activated TGF-β signaling pathway in the wound area(P<0.05 vs.controls),without altering the wound healing process.Conclusion ASPN promotes the development of ke-loid by activating TGF-β signaling pathway.
Keywords:keloidASPN proteinTGF-β pathwaycollagenPOSTN protein
Publication Date:2025-01-27
Online Publishing Date:2025-08-15(First online date of this platform, not the publication date of the document)
Pages:10( 6-15 )