Akt/mTOR integrate energy metabolism with Wnt signal to influence wound epithelium growth in Gekko Japonicus

Abstract

The formation of wound epithelium initiates regeneration of amputated tail in Gekko japonicus. Energy metabolism is indispensable for the growth of living creatures and typically influenced by temperature. In this study, we reveal that low temperature lowers energy metabolism level and inhibits the regeneration of amputated tails of Gekko japonicus. We further find that low temperature attenuates the activation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in regenerated tissues upon injury signals, and the inhibition of Akt hinders proliferation of the wound epithelium. Additionally, wingless/integrated (Wnt) inhibition suppresses epithelium proliferation and formation by inhibiting Akt activation. Finally, low temperature elevates the activity of adenylate-activated kinase (AMPK) pathway and in turn attenuates wound epithelium formation. Meanwhile, either mTOR downregulation or AMPK upregulation is associated with worse wound epithelium formation. Summarily, low temperature restricts wound epithelium formation by influencing energy sensory pathways including Akt/mTOR and AMPK signaling, which is also modulated by injury induced Wnt signal. Our results provide a mechanism that incorporates the injury signals with metabolic pathway to facilitate regeneration.

Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging

“…defined in human stem cell reprogramming (69) and zebrafish (70) as well as homeostasis, stress, cancer, metabolism, aging, and senescence (22,(71)(72)(73)(74)(75)(76). The influence of both p53 and AKT/mTOR on the Wnt pathway at the intersection of metabolism and injury was necessary for repair, and optimal repair was dependent on the coactivation of multiple pathways (50,(77)(78)(79)(80)(81). Notch signaling is also critical for the suppression of TSC2 in progenitor populations to drive lineage commitment and differentiation (21), and its intersection with Wnt drives arterial specification in the developing vasculature (82).…”