title: Non-adenine based purines accelerate wound healing.
abstract: Wound healing is a complex sequence of cellular and molecular processes that involves multiple cell types and biochemical mediators. Several growth factors have been identified that regulate tissue repair, including the neurotrophin nerve growth factor (NGF). As non-adenine based purines (NABPs) are known to promote cell proliferation and the release of growth factors, we investigated whether NABPs had an effect on wound healing. Full-thickness, excisional wound healing in healthy BALB/c mice was significantly accelerated by daily topical application of NABPs such as guanosine (50% closure by days 2.5-2.8). Co-treatment of wounds with guanosine plus anti-NGF reversed the guanosine-promoted acceleration of wound healing, indicating that this effect of guanosine is mediated, at least in part, by NGF. Selective inhibitors of the NGF-inducible serine/threonine protein kinase (protein kinase N), such as 6-methylmercaptopurine riboside abolished the acceleration of wound healing caused by guanosine, confirming that activation of this enzyme is required for this effect of guanosine. Treatment of genetically diabetic BKS.Cg-m+/+lepr db mice, which display impaired wound healing, with guanosine led to accelerated healing of skin wounds (25% closure by days 2.8-3.0). These results provide further confirmation that the NABP-mediated acceleration of cutaneous wound healing is mediated via an NGF-dependent mechanism. Thus, NABPs may offer an alternative and viable approach for the treatment of wounds in a clinical setting.
authors.affiliation: Department of Surgery, McMaster University Health Sciences Centre, 4N71B, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada, jiangs@mcmaster.ca.
authors.forename: Shucui
authors.initials: S
authors.lastname: Jiang
authors.forename: Caleb C J
authors.initials: CC
authors.lastname: Zavitz
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Amit
authors.initials: A
authors.lastname: Saraf
authors.forename: Robert
authors.initials: R
authors.lastname: Zielinski
authors.forename: James D
authors.initials: JD
authors.lastname: Ramsbottom
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ballerini
authors.forename: Iolanda
authors.initials: I
authors.lastname: D'Alimonte
authors.forename: Silvia
authors.initials: S
authors.lastname: Romano
authors.forename: Gemma
authors.initials: G
authors.lastname: Fischione
authors.forename: Ugo
authors.initials: U
authors.lastname: Traversa
authors.forename: Eva S
authors.initials: ES
authors.lastname: Werstiuk
authors.forename: Michel P
authors.initials: MP
authors.lastname: Rathbone