Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2.
Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism.


METHODS
C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis.


RESULTS
This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway.


CONCLUSION
This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.
['Bai|Yang|Y|', 'Xu|Rui|R|', 'Zhang|Xueyuan|X|', 'Zhang|Xiaorong|X|', 'Hu|Xiaohong|X|', 'Li|Yashu|Y|', 'Li|Haisheng|H|', 'Liu|Meixi|M|', 'Huang|Zhenggen|Z|', 'Yan|Rongshuai|R|', 'He|Weifeng|W|', 'Luo|Gaoxing|G|', 'Wu|Jun|J|']
D000818:Animals D002470:Cell Survival D002478:Cells, Cultured D004195:Disease Models, Animal D000078404:Epidermal Cells D004817:Epidermis D007150:Immunohistochemistry D007334:Insulin-Like Growth Factor I D019409:Interleukin-15 D008297:Male D000076225:Mechanistic Target of Rapamycin Complex 2 D051379:Mice D008810:Mice, Inbred C57BL D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D060888:Real-Time Polymerase Chain Reaction D015398:Signal Transduction D020123:Sirolimus D014945:Wound Healing
Rapamycin Akt/mTORC2 Wound healing IL-15 IGF-1