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Prostaglandin E 2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo
Author(s) -
Zhao Jingling,
Shu Bin,
Chen Lei,
Tang Jinming,
Zhang Lijun,
Xie Julin,
Liu Xusheng,
Xu Yingbin,
Qi Shaohai
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13014
Subject(s) - chemistry , in vivo , prostaglandin e , matrix metalloproteinase , hypertrophic scar , prostaglandin e2 , fibroblast , smad , prostaglandin , endocrinology , tissue inhibitor of metalloproteinase , transforming growth factor , medicine , microbiology and biotechnology , pharmacology , receptor , in vitro , biochemistry , biology , anatomy
Hypertrophic scarring is a common dermal fibroproliferative disorder characterized by excessive collagen deposition. Prostaglandin E 2 ( PGE 2 ), 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 PGE 2 remains unclear. In this study, we explored the effects of PGE 2 on TGF ‐ β 1‐treated dermal fibroblasts in terms of collagen production and to determine the regulatory pathways involved, as well as understand the antiscarring function of PGE 2 in vivo . We found that PGE 2 inhibited TGF ‐ β 1‐induced collagen synthesis by regulating the balance of matrix metalloproteinases ( MMP s) 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 ‐ β 1/Smad pathway by PGE 2 is associated with its ability to inhibit collagen synthesis. An in vivo study further confirmed that PGE 2 inhibits hypertrophic scar formation by decreasing collagen production. Our results demonstrate that the novel anti‐scarring function of PGE 2 is achieved by balancing MMPs/TIMP expression and decreasing collagen production.