ALTERATIONS IN THE BMAL1 CLOCK GENE DELAY WOUND HEALING: AN ANIMAL MODEL EXPERIMENTAL STUDY

Objective: This research aimed to evaluate the effects of the circadian clock genes in regulating wound healing (WH). Study design: Wounds were created in the dorsal skin in wild-type (WT) and BMAL1 knockout (Ko) male mice. The injury was measured daily, immediately following wounding (day 0), until wound closures were observed. For the morphologic analysis of the epithelial tongues, wounds collected at day 4 of each group were used. Quantitative analyses of BrdU-positive cells were performed by using immunohistochemistry assays. The stains for K10, pS6, and αSMA were also included in the analyses. Results: Statistically significant results were observed in the healing time between the WT mice and BMAL1 Ko mice. The epithelial migrating tongues were also reduced in size in the BMAL1 Ko group, in addition to a decrease in the number of myofibroblasts. In contrast, the number of proliferative cells was higher in WT mice. WT animals also showed higher pS6 expression. Conclusion: Overall, our results demonstrated that the absence of the BMAL1 gene negatively affects the healing time leading to delayed wound healing of the skin.