Prostaglandin E 2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo

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.