The Role and Mechanism of Transglutaminase 2 in Regulating Hippocampal Neurogenesis After Traumatic Brain Injury

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2023 Feb 25

PMID 36831225

Authors

Ruo-Xi Shi

Cong Liu

Ya-Jie Xu

Ying-Ying Wang

Bao-Dong He

Xuan-Cheng He

Hong-Zhen Du

Baoyang Hu

Jianwei Jiao

Chang-Mei Liu

Zhao-Qian Teng

Affiliations

Soon will be listed here.

Abstract

Traumatic brain injury usually results in neuronal loss and cognitive deficits. Promoting endogenous neurogenesis has been considered as a viable treatment option to improve functional recovery after TBI. However, neural stem/progenitor cells (NSPCs) in neurogenic regions are often unable to migrate and differentiate into mature neurons at the injury site. Transglutaminase 2 (TGM2) has been identified as a crucial component of neurogenic niche, and significantly dysregulated after TBI. Therefore, we speculate that TGM2 may play an important role in neurogenesis after TBI, and strategies targeting TGM2 to promote endogenous neural regeneration may be applied in TBI therapy. Using a tamoxifen-induced conditional knockout mouse line and a mouse model of stab wound injury, we investigated the role and mechanism of TGM2 in regulating hippocampal neurogenesis after TBI. We found that was highly expressed in adult NSPCs and up-regulated after TBI. Conditional deletion of resulted in the impaired proliferation and differentiation of NSPCs, while overexpression enhanced the abilities of self-renewal, proliferation, differentiation, and migration of NSPCs after TBI. Importantly, injection of lentivirus overexpressing TGM2 significantly promoted hippocampal neurogenesis after TBI. Therefore, TGM2 is a key regulator of hippocampal neurogenesis and a pivotal therapeutic target for intervention following TBI.

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