Diminished nitric oxide production following administration of transforming growth factor-beta1 using a noninflammatory wound repair model.
The effects of transforming growth factor-beta1 (TGF-beta1) on systemic nitric oxide (NO) production and wound repair were evaluated using a noninflammatory mouse perforated mesentery connective tissue repair model. Urinary nitrates were monitored as a measure of NO production. TGF-beta1 [bovine serum albumin (BSA) carrier and TGF-beta1 BSA carrier free] were administered on days 0 and 1 and were evaluated in mice over a 10-day period. A significant decrease in the average postwounding urinary nitrate levels compared to prewounding levels was observed within the TGF-beta1 treatment group animals (P </= 0.001) with an insignificant change for the phosphate-buffered saline control animals (P </= 0.10). Additionally, TGF-beta1-treated animals showed significant connective tissue repair compared to controls without a concurrent increase in postwounding urinary nitrate levels, supporting the noninflammatory nature of the perforated mesentery model. Our findings suggest that an unforseen consequence of TGF-beta1 administration is diminished basal nitric oxide production. When using TGF-beta1 in a wound repair or other therapeutic model, the administration of an exogenous NO donor compound may be necessary in order to ensure homeostasis, thereby avoiding undesired physiological consequences due to diminished basal NO production.
Bauer
J A
JA
Department of Chemistry, The University of Akron, Akron, Ohio, 44325-3601, USA.
Harr
M E
ME
Smith
D J
DJ
D000818:Animals; D003238:Connective Tissue / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008643:Mesentery / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D009566:Nitrates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide