Mechanisms of carvacrol-induced expression of type I collagen gene.
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.
Lee
Jongsung
J
Biospectrum Life Science Institute, 101-701 SK VENTIUM, 522 Dangjung Dong, Gunpo City, 435-833 Gyunggi Do, Republic of Korea.
Jung
Eunsun
E
Yu
Hyunkyung
H
Kim
Yongwoo
Y
Ha
Jaehyoun
J
Kim
Yeong Shik
YS
Park
Deokhoon
D
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
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