title: Prostaglandin E2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo.
abstract: Hypertrophic scarring is a common dermal fibroproliferative disorder characterized by excessive collagen deposition. Prostaglandin E2 (PGE2 ), an important inflammatory product synthesized via the arachidonic acid cascade, has been shown to act as a fibroblast modulator and to possess antifibroblastic activity. However, the mechanism underlying the antifibrotic effect of PGE2 remains unclear. In this study, we explored the effects of PGE2 on TGF-β1-treated dermal fibroblasts in terms of collagen production and to determine the regulatory pathways involved, as well as understand the antiscarring function of PGE2 in vivo. We found that PGE2 inhibited TGF-β1-induced collagen synthesis by regulating the balance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP). It did so by upregulating cAMP through the E prostanoid (EP)2 receptor. We determined that inhibition of the TGF-β1/Smad pathway by PGE2 is associated with its ability to inhibit collagen synthesis. An in vivo study further confirmed that PGE2 inhibits hypertrophic scar formation by decreasing collagen production. Our results demonstrate that the novel anti-scarring function of PGE2 is achieved by balancing MMPs/TIMP expression and decreasing collagen production.
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Julin
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaohai
authors.initials: S
authors.lastname: Qi
mesh_terms: D000818:Animals; D001384:Azetidines; D002921:Cicatrix / Q000517:prevention & control*; D005576:Colforsin; D003094:Collagen / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D054833:Isoindoles; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D001384:Azetidines; D054833:Isoindoles; C515270:N-(2-(4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo(f)isoindol-2-yl)phenyl)acetyl)benzene sulphonamide; D051785:Smad Proteins; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D005576:Colforsin; D003094:Collagen; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C570688:1-(4-fluorobenzoyl)-3-(((6-methoxy-2-naphthyl)oxy)methyl)azetidine-3-carboxylic acid; D015232:Dinoprostone
keywords: PGE2; collagen; scar