title: Mechanisms of carvacrol-induced expression of type I collagen gene.
abstract: BACKGROUND
  Skin aging is accompanied by wrinkle formation and appears to be principally related to decreases in the levels of type I collagen, the primary component of the dermal layer of skin.
  
  
  OBJECTIVE
  To investigate the effect of carvacrol on collagen gene expression and its mechanisms of action.
  
  
  METHODS
  To elucidate the effect of carvacrol on collagen expression and its mechanism, several experiments were performed in human dermal fibroblasts. Collagen production, small interference RNA, Ca(2+) mobilization, COL1A2/AP-1 luciferase reporter assays and Western blots for proteins that are involved in collagen gene expression were used in this study.
  
  
  RESULTS
  Carvacrol activated both the human COL1A2 promoter activity and the synthesis of human type I procollagen. Additionally, we attempted to characterize the mechanism of action of carvacrol in type I procollagen synthesis. In a human COL1A2 promoter luciferase assay, the small interference RNA for SP-1 did not reduce the carvacrol-induced promoter activation. Also, Smad 2 phosphorylation was not induced by carvacrol. However, in the AP-1 (activator protein-1) luciferase reporter assay and in the Western blot analysis for mitogen-activated protein kinases (MAPKs), carvacrol induced the activation of the AP-1 promoter and the phosphorylation of JNK and ERK1/2 (p42/44 MAPK), but did not induce the phosphorylation of p38 MAPK. Carvacrol also induced intracellular Ca(2+) mobilization and phosphorylation of phospholipase Cgamma1 (PLCgamma1), a molecule upstream of Ca(2+). In addition, PAO, a PLCgamma1 inhibitor, attenuated the carvacrol-induced production of collagen.
  
  
  CONCLUSIONS
  Our study suggests that the PLCgamma1 signaling pathway may be involved in the carvacrol-induced expression of the type I collagen gene.
authors.affiliation: Biospectrum Life Science Institute, 101-701 SK VENTIUM, 522 Dangjung Dong, Gunpo City, 435-833 Gyunggi Do, Republic of Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Hyunkyung
authors.initials: H
authors.lastname: Yu
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Jaehyoun
authors.initials: J
authors.lastname: Ha
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D000081007:Cymenes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D024042:Collagen Type I; D000081007:Cymenes; D039821:Monoterpenes; C073316:carvacrol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C522157:PLCG1 protein, human; D051966:Phospholipase C gamma; D002118:Calcium