Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts.
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.
Park
Hyun Jeong
HJ
Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. hjpark@catholic.ac.kr
Ock
Sun Myeong
SM
Kim
Hee Jung
HJ
Park
Hong Jin
HJ
Lee
Young Bok
YB
Choi
Jung Min
JM
Cho
Chul Soo
CS
Lee
Jun Young
JY
Cho
Baik Kee
BK
Cho
Dae Ho
DH
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
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