Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo

Louisa Balazs, Juraj Okolicany, Mike Ferrebee, Betsy Tolley, Gabor Tigyi


The lipid mediator lysophosphatidic acid (LPA) regulates cell proliferation and enhances cell motility in vitro, both of which are important events in wound healing. To evaluate the effects of LPA in vivo, it was applied to a full-thickness wound of rat skin. LPA in micromolar concentrations, or solvent, was applied daily. Animals were killed at 1, 3, 6, and 9 days after wounding and processed for histological evaluation, including hematoxylin-eosin staining and histochemical markers for macrophage-histiocytes, proliferating cells, and capillary endothelial cells. LPA treatment accelerated wound closing and increased neoepithelial thickness. Cytological evaluation showed no evidence for a secondary inflammation-mediated injury, infection, or increased keloid formation. Whereas LPA caused only a modest dose-dependent increase in proliferating cells, a marked increase in the immigration of histiocyte-macrophage cells was observed as early as day 1. The peaks of several cytological features and immunohistological markers preceded those of the untreated side. Our data suggest that exogenously applied LPA in this model promotes healing and that macrophage-histiocytes are the primary LPA-responsive cells in vivo.

  • lipid
  • macrophage


  • This work was supported by the National Heart, Lung, and Blood Institute Grant HL-61469 and a grant from The University of Tennessee Medical Group.

  • G. Tigyi is an Established Investigator of the American Heart Association.

  • Address for reprint requests and other correspondence: G. Tigyi, Dept. of Physiology, 894 Union Ave., Memphis, TN 38163 (E-mail:gtigyi{at}

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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