Differential regulation of free-floating collagen gel contraction by human fetal and adult dermal fibroblasts in response to prostaglandin E2 mediated by an EP2/cAMP-dependent mechanism.
In contrast to fetal wound healing, dermal adult wound healing results in imperfect repair and scar formation. Fibroblasts are responsible for the contraction and remodeling of the wound matrix, which is influenced by inflammatory mediators including prostaglandin E2 (PGE2). This study addresses the mechanism by which PGE2 regulates contraction of collagen gels by human fetal and adult dermal fibroblasts. We hypothesized that the intrinsic phenotypic properties of the two types of fibroblasts and their responses to PGE2 alter their contraction properties and contribute to different wound healing outcomes. Contraction was evaluated using free-floating fibroblast-populated collagen gels that contract by migratory forces. PGE2 was found to differentially inhibit collagen gel contraction by fetal and adult fibroblasts. This effect was mimicked by a specific PGE2 receptor agonist as well as by two pharmacological agents, indicating a cyclic adenosine monophosphate-dependent signaling pathway mediated through the EP2 receptor. Our results indicate that fetal fibroblast contraction is maintained by a more stable actin cytoskeleton. Therefore, the migratory phenotype may be sufficient for physical remodeling of the wound matrix leading to regenerative repair. Maintenance of this phenotype in the later stages of wound healing could potentially be achieved by targeting cyclic adenosine monophosphate via the EP2 receptor.
Parekh
Aron
A
Pittsburgh Tissue Engineering Initiative; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sandulache
Vlad C
VC
Lieb
Audrey S
AS
Dohar
Joseph E
JE
Hebda
Patricia A
PA
D000704:Analysis of Variance; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D005782:Gels; D006801:Humans; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology*
D005782:Gels; D003094:Collagen; D000242:Cyclic AMP; D015232:Dinoprostone