Potential mechanism of TMEM2/CD44 in endoplasmic reticulum stress-induced neuronal apoptosis in a rat model of traumatic brain injury

Traumatic brain injury (TBI) can lead to the disruption of endoplasmic reticulum (ER) homeostasis in neurons and induce ER stress. Transmembrane protein 2 (TMEM2) may regulate ER stress through the p38/ERK signaling pathway, independent of the classic unfolded protein response (UPR) pathway. The present study examined the expression of TMEM2 following TBI in a rat model, in an aim to determine whether the mitogen-activated protein kinase (MAPK) signaling pathway is controlled by TMEM2/CD44 to mitigate secondary brain injury. For this purpose, 89 Sprague-Dawley rats were used to establish the model of TBI, and TMEM2 siRNA was used to silence TMEM2. Western blot analysis, immunofluorescence, TUNEL assay and Fluoro-Jade C staining, the wet-dry method and behavioral scoring were used for analyses. The results revealed that TMEM2 was activated following TBI in rats. The silencing of TMEM2 resulted in a significant increase in the levels of p38 and ERK (components of MAPK signaling), while brain edema, neuronal apoptosis and degeneration were significantly aggravated. TBI increased TMEM2/CD44-aggravated brain edema and neurological impairment, possibly by regulating ERK and p38 signaling. TMEM2/CD44 may thus be a target for the prevention and control of TBI.