Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper.
Copper is essential to wound healing as well as a widespread environmental pollutant, with skin aging potential. Wound healing and skin aging are facilitated by matrixmetalloproteinases (MMP), which remodel the extracellular matrix, and interleukin-8 (IL-8), linked with copper. This research investigated the mechanism to copper's role in wound healing or skin aging by regulation of MMP-1 and IL-8 genes. It examined the dose-responsive effects of copper on MMP-1, -2, and -9 activities; MMP-1 and IL-8 gene regulation at protein, mRNA, and promoter levels; tissue inhibitor of matrixmetalloproteinases-1 (TIMP-1) expression; and cell proliferation. Copper stimulated cell proliferation and the expression of MMP-1 and IL-8 genes at the protein, mRNA, and promoter levels, indicating transcriptional regulation, without significantly altering TIMP-1. The research suggests that copper facilitates wound healing as well as skin aging via the induction of MMP-1 expression, with limiting MMP effect at the higher concentrations through enhanced IL-8 expression, which favors extracellular matrix deposition.
Philips
Neena
N
School of Natural Sciences, Fairleigh Dickinson University, Teaneck, New Jersey 07666, USA. nphilips@fdu.edu
Hwang
Hyeondo
H
Chauhan
Sagar
S
Leonardi
Donna
D
Gonzalez
Salvador
S
D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
D004785:Environmental Pollutants; D016209:Interleukin-8; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003300:Copper; D020781:Matrix Metalloproteinase 1