Details
- Autor(en) / Beteiligte
- Titel
- Oxidant exposure induces cysteine-rich protein 61 (CCN1) via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts
- Ist Teil von
- PloS one, 2014-12, Vol.9 (12), p.e115402
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0115402Titel-ID: cdi_plos_journals_1640006942
- Format
- –
- Schlagworte
- Activator protein 1, Adult, Aging, Antioxidants, Antioxidants (Nutrients), Antioxidants - pharmacology, Base Sequence, Binding Sites, Biology and Life Sciences, c-Jun protein, Cells, Cultured, Collagen, Collagen (type I), Collagen Type I - metabolism, Connective tissues, Cysteine, Cysteine-Rich Protein 61 - metabolism, Cystine, Dermatology, Dermis - cytology, Fibroblasts, Fibroblasts - drug effects, Fibroblasts - metabolism, Fibroblasts - radiation effects, Gene expression, Growth factors, Humans, Hydrogen peroxide, Intracellular Space - drug effects, Intracellular Space - metabolism, Kinases, Medical schools, Middle Aged, Molecular Sequence Data, N-Acetyl-L-cysteine, Oxidants - pharmacology, Oxidative stress, Oxidative Stress - drug effects, Oxidative Stress - radiation effects, Oxygen, Promoter Regions, Genetic - genetics, Protein Binding - drug effects, Protein Binding - radiation effects, Proteins, Reactive oxygen species, Reactive Oxygen Species - metabolism, Skin, Studies, Thiols, Transcription Factor AP-1 - metabolism, Transcription factors, Ultraviolet Rays, Young Adult