title: A novel role of peripheral corticotropin-releasing hormone (CRH) on dermal fibroblasts.
abstract: Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh-/-) had higher proliferation and migration rates and compromised production of IL-6 and TGF-β1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF(1) antagonist antalarmin recapitulated the findings in the Crh-/- cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis.
authors.affiliation: Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Rassouli
authors.forename: George
authors.initials: G
authors.lastname: Liapakis
authors.forename: Iakovos
authors.initials: I
authors.lastname: Lazaridis
authors.forename: George
authors.initials: G
authors.lastname: Sakellaris
authors.forename: Kostas
authors.initials: K
authors.lastname: Gkountelias
authors.forename: Achille
authors.initials: A
authors.lastname: Gravanis
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Margioris
authors.forename: Katia P
authors.initials: KP
authors.lastname: Karalis
authors.forename: Maria
authors.initials: M
authors.lastname: Venihaki
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency / Q000378:metabolism*; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015850:Interleukin-6; D018019:Receptors, Corticotropin-Releasing Hormone; D053773:Transforming Growth Factor beta1; D003346:Corticotropin-Releasing Hormone