Rapamycin and Wound Healing: mTOR inhibits autophagy to facilitate cell swelling and rapid wound repair

New lab pre-print!! Rapamycin is effective, but it slows down surgical recovery. Here, we use our wound healing model in the Drosophila embryo to ask why.

Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the swelling of the cells adjacent to the wound. The mechanistic target of rapamycin complex 1 (mTORC1) is often associated with cell growth. We found that disrupting mTORC1 signalling prevented cell swelling and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Using five-dimensional time-lapse microscopy, as well as pharmacological and genetic manipulations, we demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. Quantitative image analysis showed that mTOR inhibition increased autophagy, and that activating autophagy prevented cell swelling and slowed down embryonic wound closure. Finally, reducing autophagy in embryos in which mTORC1 signalling was disrupted rescued rapid wound repair. Together, our results show that mTORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.


Not quite sure how this study advances our existing knowledge of wound healing. Authors of the study the first three statements/premises are: the first about embryo wound repair without scarring (known) and the second about cell swelling ( is this their contribution? ) and the third about mtorc1 implication in cell growth (known) . So they found that mtorc1 suppression slows down the cell swelling and wound healing. Great. I believe we all already knew that rapamycin slows down wound healing as there are a few research studies on the subject already. Are they making a claim that if you disrupt mtorc1 you won’t get embryo like healing? If so they need to prove it in both embryo mice and then in adult mice. For now as I see it no conclusions can be made.

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