The role of iNOS in wound healing.
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 ([(3)H]-thymidine incorporation) and collagen synthesis ([(3)H]-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 fibroblast-populated collagen lattices.


RESULTS
iNOS-KO fibroblasts proliferated more slowly, synthesized less collagen, and contracted fibroblast-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.
Shi
H P
HP
Department of Surgery, Sinai Hospital of Baltimore, MD 21215, USA.
Most
D
D
Efron
D T
DT
Tantry
U
U
Fischel
M H
MH
Barbul
A
A
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D014945:Wound Healing / Q000502:physiology*
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D003094:Collagen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010396:Penicillamine