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

Wu,Muyao; Wang,Chaoyu; Gong,Yating; Huang,Yaqian; Jiang,Lei; Zhang,Min; Gao,Rong; Dang,Baoqi

doi:10.3892/ijmm.2023.5322

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

Authors:
- Muyao Wu
- Chaoyu Wang
- Yating Gong
- Yaqian Huang
- Lei Jiang
- Min Zhang
- Rong Gao
- Baoqi Dang
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Affiliations: Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, P.R. China, Department of Preventive Treatment, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, P.R. China, Department of Neurosurgery, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China
Published online on: October 24, 2023 https://doi.org/10.3892/ijmm.2023.5322
Article Number: 119
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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