Transglutaminase 2 regulates terminal erythroid differentiation via cross-linking activity

Yingying Zhang; Lifang Shi; Ke Yang; Xuehui Liu; Xiang Lv

doi:10.3389/fcell.2023.1183176

Transglutaminase 2 regulates terminal erythroid differentiation via cross-linking activity

Front Cell Dev Biol. 2023 Apr 24:11:1183176. doi: 10.3389/fcell.2023.1183176. eCollection 2023.

Authors

Yingying Zhang¹, Lifang Shi^{1

2}, Ke Yang¹, Xuehui Liu¹, Xiang Lv¹

Affiliations

¹ State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Changping Center for Disease Control and Prevention, Beijing, China.

Abstract

Transglutaminase 2 (TGM2) is a versatile enzyme that modulates cell survival and differentiation. However, its role in terminal erythroid differentiation is poorly understood. In this study, we investigated the function of TGM2 in primary fetal liver erythroid differentiation. We predicted TGM2 as an upstream regulator via ingenuity pathway analysis (IPA), and found that its expression was increased at both RNA and protein level during terminal erythroid differentiation. TGM2 cross-linking activity inhibitors GK921 and Z-DON suppressed erythroid maturation and enucleation, while its GTPase inhibitor LDN27219 had no such effect. Z-DON treatment arrested differentiation at basophilic erythroblast stage, and interfered with cell cycle progression. RT-PCR demonstrated decreased GATA-1 and KLF1, and disarranged cyclin, CDKI and E2F family genes expression after Z-DON treatment. In conclusion, TGM2 regulates terminal erythroid differentiation through its cross-linking enzyme activity.

Keywords: TGM2; cell cycle; cross-linking activity; erythroid differentiation; fetal liver.

Grants and funding

This research was supported by CAMS Innovation Fund for Medical Sciences (CIFMS, grant 2021-I2M-1-019), National Natural Science Foundation of China (grant 82170120), Haihe Laboratory of Cell Ecosystem Innovation Fund (22HHXBSS00008), CAMS Innovation Fund for Medical Sciences (CIFMS, grant 2019-I2M-1-004), and State Key Laboratory Special Fund 2060204.