Hormônio alfa-melanócito estimulante melhora a cicatrização de feridas cutâneas em camundongos

Abstract

Skin wound healing in adult mammals frequently result in scar tissue formation where collagen replaces the original tissue, whereas wound closure in fetal skin heals with regeneration of the original tissue. Reduction or alteration in the inflammatory cell composition after wound has been correlated with regeneration or reduction of scar tissue formation. Alpha-melanocyte stimulating hormone (-MSH) is produced in the central nervous system as well as by immune cells or in the skin where it can stimulate eumelanin production. The action of -MSH is mediated by melanocortins receptors (MC-R1 and MC-R4) expressed on skin cells, macrophages, mast cells and T-lymphocytes. Agouti is one antagonist of MC-R1 and MC-R4 and binding of agouti to these skin receptors inhibits eumelanin production. Alpha-MSH also has broad anti-inflammatory effects inhibiting the production of pro-inflammatory cytokines, prostaglandins and histamine. We tested if the intraperitoneal injection of -MSH or agouti, 30 minutes before skin lesion in C57BL/6 adult mice, would alter the inflammatory infiltrate and extracellular matrix deposition as observed 3 and 40 days after lesion. The injection of 125 mg/Kg of agouti did not change leukocyte (mean ± SEM - agouti 4,12 ± 0,28 vs control 4,64 ± 0,34) or mast cell (agouti 11,0 ± 1,22 vs control 9,5 ± 0,95) numbers 3 days after the lesion. Nor did the injection of agouti change scar area measured macroscopically (agouti 11,78 ± 0,48 vs control 12,92 ±1,05) or microscopically (agouti 0,30 ± 0,03 vs control 0,33 ± 0,02) 40 days after the lesion. However, the injection of 1,0 mg/kg of -MSH significantly reduced leukocyte (-MSH 2,05 ± 0,06 vs control 4,64 ± 0,34) and mast cell (-MSH 5,5 ± 0,27 vs control 9,5 ±0,95) counts 3 days after the lesion and also reduced scar area 40 days after the lesion measured either macroscopically (-MSH 9,24 ± 0,65 vs control 12,92 ± 1,05) or microscopically (-MSH 0,22 ± 0,01 vs control 0,33 ± 0,02). In addition, -MSH injection resulted in better collagen deposition, increased collagen III (-MSH 0,78 ± 0,1 vs control 0,51 ± 0,06) without alteration in collagen I (-MSH 0,55 ± 0,05 vs control 0,60 ± 0,1), 40 days after the lesion.