title: Esculetin promotes type I procollagen expression in human dermal fibroblasts through MAPK and PI3K/Akt pathways.
abstract: Type I collagen is the major constituent of the skin and the reduction of dermal type I collagen content is closely associated with the intrinsic skin aging. We here found that esculetin, 6,7-dihydroxycoumarin, strongly induces type I procollagen expression in human dermal fibroblasts. Esculetin not only increased protein levels of type I procollagen but also increased mRNA levels of COL1A1 but not COL1A2. Esculetin activated the MAPKs (ERK1/2, p38, JNK) and PI3K/Akt pathways, through which it promoted the type I procollagen expression. We also demonstrated that the binding motifs for transcription factor Sp1 occur with the highest frequency in the COL1A1 promoter and that esculetin increases the Sp1 expression through the MAPK and PI3K/Akt pathways. These results suggest that esculetin promotes type I procollagen expression through the MAPK and PI3K/Akt pathways and that Sp1 might be involved in the esculetin-induced type I procollagen expression via activation of the COL1A1 transcription.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Jung Hae
authors.initials: JH
authors.lastname: Park
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: An
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Kim
authors.forename: Myeon
authors.initials: M
authors.lastname: Choe
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Han
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D000090602:Collagen Type I, alpha 1 Chain; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016329:Sp1 Transcription Factor; D014468:Umbelliferones; C007628:esculetin