Does rat granulation tissue maturation involve gap junction communications?
BACKGROUND
Wound healing, a coordinated process, proceeds by sequential changes in cell differentiation and terminates with the deposition of a new connective tissue matrix, a scar. Initially, there is the migratory fibroblast, followed by the proliferative fibroblast, then the synthetic fibroblast, which transforms into the myofibroblast, and finally the apoptotic fibroblast. Gap junction intercellular communications are proposed to coordinate the stringent control of fibroblast phenotypic changes. Does added oleamide, a natural fatty acid that blocks gap junction intercellular communications, alter the phenotypic progression of wound fibroblasts?


METHODS
Pairs of polyvinyl alcohol sponges attached to Alzet pumps, which constantly pumped either oleamide or vehicle solvent, were implanted subcutaneously into three rats. On day 8, implants were harvested and evaluated histologically and biochemically.


RESULTS
The capsule of oleamide-treated sponge contained closely packed fibroblasts with little connective tissue between them. The birefringence intensity of that connective tissue was reduced, indicating a reduced density of collagen fiber bundles. Myofibroblasts, identified immunohistologically by alpha-smooth muscle actin-stained stress fibers, were reduced in oleamide-treated implants. Western blot analysis showing less alpha-smooth muscle actin confirmed the reduced density of myofibroblasts.


CONCLUSIONS
It appears that oleamide retards the progression of wound repair, where less connective tissue is deposited, the collagen is less organized, and the appearance of myofibroblasts is impaired. These findings support the hypothesis that gap junction intercellular communications between wound fibroblasts in granulation tissue play a role in the progression of repair and the maturation of granulation tissue into scar.
Au
Katherine
K
Hershey, Pa. From the Irving S. Zubar Plastic Surgery Laboratory, Division of Plastic Surgery, Milton S. Hershey Medical Center.
Ehrlich
H Paul
HP
D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000473:pathology / Q000502:physiology*; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology
D009829:Oleic Acids; C029407:oleylamide