title: Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts.
abstract: Vitamin C is used as an anti-ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL-37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL-37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL-37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL-37. Vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37.
authors.affiliation: Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. hjpark@catholic.ac.kr
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Sun Myeong
authors.initials: SM
authors.lastname: Ock
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hong Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Baik Kee
authors.initials: BK
authors.lastname: Cho
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Cho
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007627:Keloid / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D001205:Ascorbic Acid; D054804:Cathelicidins