title: Smad interacting protein 1 as a regulator of skin fibrosis in pathological scars.
abstract: Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by the excessive and abnormal deposition of collagen-based extracellular matrix (ECM) components. However, the molecular basis of keloid and hypertrophic scar formation has not been fully elucidated. Here, we demonstrated that down-regulation of the transcription factor Smad interacting protein 1 (SIP1) could be relevant to keloid and hypertrophic scar formation. The results of the present study show that the level of SIP1 mRNA is significantly decreased in pathological scar tissues and in normal skin and pathological scar fibroblasts treated with transforming growth factor β1 (TGF-β1). In contrast, the expression of SIP1 mRNA is not decreased in normotrophic scar samples. The SIP1 mRNA level inversely correlates with the mRNA level of type I collagen (COL1A2) and directly correlates with the mRNA level of matrix metalloproteinase-1 (MMP1). Overexpression of SIP1 in keloid and hypertrophic scar fibroblasts represses TGF-β1-stimulated COL1A2 expression and induces MMP1 expression. Alternatively, knockdown of SIP1 in normal skin fibroblasts enhance TGF-β1-induced COL1A2 levels. These findings suggest that SIP1 could be a regulator of skin fibrosis, and depletion of SIP1 in pathological scar tissues could result in an up-regulation of collagen and down-regulation of matrix metalloproteinase, leading to an abnormal accumulation of ECM along with fibrosis and pathological scar formation.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Zhan-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Zhang
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shi
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liu
authors.forename: Zhou-Ting
authors.initials: ZT
authors.lastname: Zhao
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Wang
authors.forename: Xiao-Zhi
authors.initials: XZ
authors.lastname: Bai
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Cai
authors.forename: Hua-Yu
authors.initials: HY
authors.lastname: Zhu
authors.forename: Chao-Wu
authors.initials: CW
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002921:Cicatrix / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007627:Keloid / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D012867:Skin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C411545:SNIP1 protein, human; D016212:Transforming Growth Factor beta; D003094:Collagen; D020781:Matrix Metalloproteinase 1