REVERSAL OF IMPAIRED WOUND REPAIR IN INOS-DEFICIENT MICE BY TOPICAL ADENOVIRAL-MEDIATED INOS GENE-TRANSFER

Most evidence indicates that nitric oxide plays a role in normal wound repair; however, involvement of inducible nitric oxide synthase (iNOS ) has not been established. Experiments were carried out to determine the requirement for iNOS in closing excisional wounds, Wound closure w as delayed by 31% in iNOS knockout mice compared with wildtype animals , An identical delay in wound closure was observed in wild-type mice g iven a continuous infusion of the partially selective iNOS inhibitor N -6-(iminoethyl)-L-lysine. Delayed wound healing in iNOS-deficient mice was completely reversed by a single application of an adenoviral vect or containing human iNOS cDNA (AdiNOS) at the time of wounding. Revers e transcription PCR identified iNOS mRNA expression in wild-type mice peaking 4-6 d after wounding, and confirmed expression of human iNOS i n the adenoviral vector containing human iNOS cDNA-treated animals, Th ese results establish the key role of iNOS in wound closure, and sugge st a gene therapy strategy to improve wound healing in iNOS-deficient states such as diabetes, and during steroid treatment.