Progranulin is a mediator of the wound response

Abstract

Annually, 1.25 million individuals suffer burns in the United States and 6.5 million experience chronic skin ulcers, often from diabetes, pressure or venous stasis. Growth factors are essential mediators of wound repair, but their success as therapeutics in wound treatment has, so far, been limited. Therefore, there is a need to identify new wound-response regulatory factors, but few have appeared in recent years. Progranulin (also called granulin or epithelin precursor, acrogranin or PC-derived growth factor) is a growth factor involved in tumorigenesis and development. Peptides derived from progranulin have been isolated from inflammatory cells, which led to suggestions that progranulin gene products are involved in the wound response, but this remains undemonstrated. We report that in murine transcutaneous puncture wounds, progranulin mRNA is expressed in the inflammatory infiltrate and is highly induced in dermal fibroblasts and endothelia following injury. When applied to a cutaneous wound, progranulin increased the accumulation of neutrophils, macrophages, blood vessels and fibroblasts in the wound. It acts directly on isolated dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures. Progranulin is, therefore, a probable wound-related growth factor.