Yang Bai1,2, Rui Xu3, Xueyuan Zhang2, Xiaorong Zhang1, Xiaohong Hu1, Yashu Li1, Haisheng Li1, Meixi Liu1, Zhenggen Huang1, Rongshuai Yan1, Weifeng He1, Gaoxing Luo1, Jun Wu1,4. 1. State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Key Laboratory for Proteomics Disease, Institute of Burn Research, Southwest Hospital, The Third Military Medical University, Chongqing, China. 2. Department of Otolaryngology, Southwest Hospital, The Third Military Medical University, Chongqing, China. 3. Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China. 4. Department of Burns, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Abstract
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.
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.
Authors: Chloé Roffay; Guillaume Molinard; Kyoohyun Kim; Marta Urbanska; Virginia Andrade; Victoria Barbarasa; Paulina Nowak; Vincent Mercier; José García-Calvo; Stefan Matile; Robbie Loewith; Arnaud Echard; Jochen Guck; Martin Lenz; Aurélien Roux Journal: Proc Natl Acad Sci U S A Date: 2021-11-23 Impact factor: 11.205