PMID- 37900967
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231031
IS  - 1687-966X (Print)
IS  - 1687-9678 (Electronic)
VI  - 2023
DP  - 2023
TI  - Transglutaminase 2 Prevents Premature Senescence and Promotes Osteoblastic 
      Differentiation of Mesenchymal Stem Cells through NRF2 Activation.
PG  - 8815888
LID - 10.1155/2023/8815888 [doi]
LID - 8815888
AB  - Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, 
      GTPase, kinase, and protein disulfide isomerase (PDI) activities. Of these, 
      transamidase-mediated modification of proteins regulates apoptosis, 
      differentiation, inflammation, and fibrosis. TG2 is highly expressed in 
      mesenchymal stem cells (MSCs) compared with differentiated cells, suggesting a 
      role of TG2 specific for MSC characteristics. In this study, we report a new 
      function of TG2 in the regulation of MSC redox homeostasis. During in vitro MSC 
      expansion, TG2 is required for cell proliferation and self-renewal by preventing 
      premature senescence but has no effect on the expression of surface antigens and 
      oxidative stress-induced cell death. Moreover, induction of differentiation 
      upregulates TG2 that promotes osteoblastic differentiation. Molecular analyses 
      revealed that TG2 mediates tert-butylhydroquinone, but not sulforaphane, -induced 
      nuclear factor erythroid 2-related factor 2 (NRF2) activation in a transamidase 
      activity-independent manner. Differences in the mechanism of action between two 
      NRF2 activators suggest that PDI activity of TG2 may be implicated in the 
      stabilization of NRF2. The role of TG2 in the regulation of antioxidant response 
      was further supported by transcriptomic analysis of MSC. These results indicate 
      that TG2 is a critical enzyme in eliciting antioxidant response in MSC through 
      NRF2 activation, providing a target for optimizing MSC manufacturing processes to 
      prevent premature senescence.
CI  - Copyright (c) 2023 Soo-Jin Lee et al.
FAU - Lee, Soo-Jin
AU  - Lee SJ
AUID- ORCID: 0000-0001-5520-6522
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Shin, Ji-Woong
AU  - Shin JW
AUID- ORCID: 0000-0002-2405-2740
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Kwon, Mee-Ae
AU  - Kwon MA
AUID- ORCID: 0000-0001-9177-4279
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Lee, Ki Baek
AU  - Lee KB
AUID- ORCID: 0000-0002-0208-272X
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Laboratory for Cellular Response to Oxidative Stress, Cell2in, Inc., Seoul, 
      Republic of Korea.
FAU - Kim, Hyo-Jun
AU  - Kim HJ
AUID- ORCID: 0000-0002-9818-6661
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Lee, Jin-Haeng
AU  - Lee JH
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Kang, Heun-Soo
AU  - Kang HS
AUID- ORCID: 0000-0003-4903-7149
AD  - Laboratory for Cellular Response to Oxidative Stress, Cell2in, Inc., Seoul, 
      Republic of Korea.
FAU - Jun, Jong Kwan
AU  - Jun JK
AUID- ORCID: 0000-0002-0242-1736
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Cho, Sung-Yup
AU  - Cho SY
AUID- ORCID: 0000-0002-2720-6952
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
AD  - Medical Research Center, Genomic Medicine Institute, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Kim, In-Gyu
AU  - Kim IG
AUID- ORCID: 0000-0002-0751-4288
AD  - Department of Biochemistry and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
AD  - Institute of Human-Environment Interface Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20231020
PL  - United States
TA  - Stem Cells Int
JT  - Stem cells international
JID - 101535822
PMC - PMC10611545
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2023/10/30 06:47
MHDA- 2023/10/30 06:48
PMCR- 2023/10/20
CRDT- 2023/10/30 04:42
PHST- 2023/01/27 00:00 [received]
PHST- 2023/07/31 00:00 [revised]
PHST- 2023/09/12 00:00 [accepted]
PHST- 2023/10/30 06:48 [medline]
PHST- 2023/10/30 06:47 [pubmed]
PHST- 2023/10/30 04:42 [entrez]
PHST- 2023/10/20 00:00 [pmc-release]
AID - 10.1155/2023/8815888 [doi]
PST - epublish
SO  - Stem Cells Int. 2023 Oct 20;2023:8815888. doi: 10.1155/2023/8815888. eCollection 
      2023.