USP11 exacerbates neuronal apoptosis after traumatic brain injury via PKM2-mediated PI3K/AKT signaling pathway

Ubiquitin-specific protease 11 (USP11) is a ubiquitin-specific protease involved in the regulation of protein ubiquitination. However, its role in traumatic brain injury (TBI) remains unclear. This experiment suggests that USP11 is possibly involved in regulating neuronal apoptosis in TBI. Therefore, we use precision impactor device to established a TBI rat model and assayed the role of USP11 by overexpressing and inhibiting USP11. We found that Usp11 expression increased after TBI. In addition, we hypothesized that pyruvate kinase M2 (PKM2) is a potential USP11 target and experimentally confirmed that upregulation of Usp11 increased Pkm2 expression. Furthermore, elevated USP11 levels exacerbate blood-brain barrier damage, brain edema, and neurobehavioral impairment and cause apoptosis induction through Pkm2 upregulation. Moreover, we hypothesize that PKM2-induced neuronal apoptosis is mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Our findings were confirmed by changes in Pi3k and Akt expression with Usp11 upregulation and downregulation and PKM2 inhibition. In conclusion, our findings show that USP11 exacerbates injury in TBI through PKM2 and causes neurological impairment and neuronal apoptosis through the PI3K/AKT signaling pathway.