Beta 2-adrenergic receptor activation delays dermal fibroblast-mediated contraction of collagen gels via a cAMP-dependent mechanism.
Dermal fibroblasts actively contribute to wound healing by migrating to the wound, synthesizing extracellular matrices, and generating mechanical forces within the wound to initiate wound contraction. Fibroblast-seeded collagen gels provide an in vitro model to study wound contraction. The authors are evaluating the role of the adrenergic signaling system in cutaneous wound repair and recently found that beta2-adrenergic receptor (beta2-AR) activation markedly decreases keratinocyte migration, an essential step in wound reepithelialization. Because the beta2-ARs are also expressed on dermal fibroblasts, a study was initiated to determine the effects of beta-adrenergic agonists on dermal fibroblast-mediated collagen gel contraction. A beta-agonist (isoproterenol) delayed gel contraction in a dose-dependent manner. A beta2-AR specific antagonist (ICI 118,551) prevented the delay, indicating that the beta2-AR alone mediated the delay. The active cyclic adenosine monophosphate (cAMP) analog also delayed collagen gel contraction, whereas an inactive cAMP analog partially prevented the delay, suggesting that the mechanism for beta-AR agonist-mediated delay was partly cAMP-dependent. Identifying and characterizing agents that modulate wound contraction improves understanding of the wound healing process and could result in novel therapeutic strategies for preventing unwanted wound contraction in burn and trauma patients.
Pullar
Christine E
CE
Department of Dermatology, University of California Davis, Davis, California. cepullar@ucdavis.edu
Isseroff
R Rivkah
RR
D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP; D020405:Dermis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005782:Gels; D006801:Humans; D007231:Infant, Newborn; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology*
D005782:Gels; D018343:Receptors, Adrenergic, beta-2; D003094:Collagen; D000242:Cyclic AMP