title: Oxidant exposure induces cysteine-rich protein 61 (CCN1) via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts.
abstract: Human skin is a primary target of oxidative stress from reactive oxygen species (ROS) generated from both extrinsic and intrinsic sources. Oxidative stress inhibits the production of collagen, the most abundant protein in skin, and thus contributes to connective tissue aging. Here we report that cysteine-rich protein 61 (CCN1), a negative regulator of collagen production, is markedly induced by ROS and mediates loss of type I collagen in human dermal fibroblasts. Conversely, antioxidant N-acetyl-L-cysteine significantly reduced CCN1 expression and prevented ROS-induced loss of type I collagen in both human dermal fibroblasts and human skin in vivo. ROS increased c-Jun, a critical member of transcription factor AP-1 complex, and increased c-Jun binding to the AP-1 site of the CCN1 promoter. Functional blocking of c-Jun significantly reduced CCN1 promoter and gene expression and thus prevented ROS-induced loss of type I collagen. Targeting the c-Jun/CCN1 axis may provide clinical benefit for connective tissue aging in human skin.
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Robichaud
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Taihao
authors.initials: T
authors.lastname: Quan
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism*; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D055515:Cysteine-Rich Protein 61; D016877:Oxidants; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1