HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8  

作　　者：Fang Ma Honglin Liu Tongtong Xia Zhenghao Zhang Shengchao Ma Yinju Hao Jiangyong Shen Yideng Jiang Nan Li 

机构地区：[1]School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China [2]NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,China [3]Ningxia Key Laboratory of Vascular Injury and Repair Research,Ningxia Medical University,Yinchuan 750004,China [4]General Hospital of Ningxia Medical University,Yinchuan 750004,China [5]Clinical Medical School,Ningxia Medical University,Yinchuan 750004,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第3期440-451,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(No.82360628);the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2019PT330002);the Key Research and Development Projects in Ningxia Hui Autonomous Region(No.2022BFH02013).

摘　　要：Hypertrophic scar(HS)is one of the most common sequelae of patients,especially after burns and trauma.The roles of regulatory long noncoding RNAs(lncRNAs)in mediating HS remain underexplored.Human hypertrophic scarderived fibroblasts(HSFBs)have been shown to exert more potent promoting effects on extracellular matrix(ECM)accumulation than normal skin-derived fibroblasts(NSFBs)and are associated with enhanced HS formation.The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms.LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA(HSFAS).HSFAS overexpression significantly induces fibroblast proliferation,migration,and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs,while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation,migration,and myofibroblast trans-differentiation of HSFBs.Mechanistically,HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8(ADAMTS8).ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation,migration,myofibroblast trans-differentiation and apoptosis.Thus,our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function.Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.

关 键 词：FIBROBLAST HSFAS hypertrophic scar TRANS-DIFFERENTIATION 

分 类 号：R619.6[医药卫生—外科学]