Background. We have previously shown that the blockade of nitric oxide (NO) synthesis impairs wound healing, in particular collagen synthesis. Conversely, impaired wound healing is accompanied by decreased wound NO synthesis. Fibroblast collagen synthesis, proliferation, and fibroblast-mediated matrix contraction are critical to wound healing. We examined the wound healing-related phenotypic changes that are induced by the loss of inducible nitric oxide synthase (iNOS) gene function in fibroblasts. Methods. Dermal fibroblasts were obtained from 8- to 12-week-old iNOS-knock out (KO; C57BL/Ai-[KO] Nos2 N5) and wild type mice by an explant technique and used after 1 to 3 passages. Proliferation ([3H]-thymidine incorporation) and collagen synthesis ([3H] proline incorporation into collagenase-sensitive protein) were studied after stimulation with 10% fetal bovine serum. Matrix remodeling was assessed by the measurement of the contraction of fibroblasts-populated collagen lattices. Results. iNOS-KO fibroblasts proliferated more slowly, synthesized less collagen, and contracted fibro-blasts-populated collagen lattices more slowly than wild-type fibroblast. Collagen synthesis was restored to normal in KO fibroblasts in response to NO donors (s-nitroso-N-acetylpenicillamine). Conclusions. iNOS deficiency causes significant impairment in wound healing-related properties of fibroblasts, which suggests that NO plays an important role in wound healing.
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