PMID- 35525026
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20231101
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 53
DP  - 2022 Jul
TI  - MG53 protein rejuvenates hUC-MSCs and facilitates their therapeutic effects in AD 
      mice by activating Nrf2 signaling pathway.
PG  - 102325
LID - S2213-2317(22)00097-0 [pii]
LID - 10.1016/j.redox.2022.102325 [doi]
LID - 102325
AB  - Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is 
      a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in 
      vitro easily exhibit replicative senescence, which restricts their application. 
      Although MG53 protein demonstrates multiple roles for a variety of cells and 
      tissues repair, it remains unknown whether MG53 could rejuvenate senescent 
      hUC-MSCs and enhance their efficacy in AD model. Here, we firstly presented that 
      MG53 reinstated senescent hUC-MSCs via the activation of the Nrf2 signaling 
      pathway by increasing cell proliferation and migration, ameliorating senescence 
      and oxidative stress, and decreasing the release of senescence-associated 
      secretory phenotype. In vivo studies showed that MG53 treatment improved the 
      therapeutic effect of senescent hUC-MSCs in AD mice. Furthermore, MG53 combined 
      with young hUC-MSCs transplantation alleviated cognitive deficit and 
      depression-like behavior in AD mice, reduced Abeta deposition and Tau 
      phosphorylation, promoted neurogenesis, and inhibited glia cells activation and 
      oxidative stress by activating the Nrf2 signaling. Moreover, these 
      neuroprotective effects mediated by MG53 and hUC-MSCs were partly reversed by 
      Brusatol, a specific inhibitor of Nrf2 signaling. Taken together, our study 
      revealed that MG53 could rejuvenate senescent hUC-MSCs and facilitate their 
      efficacy in AD mice at least partly through activating Nrf2 signaling pathway, 
      which suggest that the combined therapy of MG53 and hUC-MSCs may be a novel and 
      effective strategy for AD.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Ma, Shanshan
AU  - Ma S
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China; 
      NHC Key Laboratory of Birth Defects Prevention, Henan Institute of Reproduction 
      Health Science and Technology, Zhengzhou, 450002, Henan, China; Institute of 
      Neuroscience, Zhengzhou University, Zhengzhou, 450052, China. Electronic address: 
      mss@zzu.edu.cn.
FAU - Zhou, Xinkui
AU  - Zhou X
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
FAU - Wang, Yaping
AU  - Wang Y
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
FAU - Li, Zhe
AU  - Li Z
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
FAU - Wang, Yingying
AU  - Wang Y
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
FAU - Shi, Jijing
AU  - Shi J
AD  - Key Medical Laboratory of Stem Cell Transformation and Application, The First 
      People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
FAU - Guan, Fangxia
AU  - Guan F
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China; 
      NHC Key Laboratory of Birth Defects Prevention, Henan Institute of Reproduction 
      Health Science and Technology, Zhengzhou, 450002, Henan, China; Institute of 
      Neuroscience, Zhengzhou University, Zhengzhou, 450052, China; Key Medical 
      Laboratory of Stem Cell Transformation and Application, The First People's 
      Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China. Electronic address: 
      guanfx@zzu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220430
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (MG53 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - *Alzheimer Disease/metabolism/therapy
MH  - Animals
MH  - Membrane Proteins/metabolism
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism
MH  - Signal Transduction
MH  - Umbilical Cord/metabolism
PMC - PMC9079718
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Human umbilical cord-derived mesenchymal stem cells
OT  - MG53 protein
OT  - Nrf2 signaling pathway
OT  - Senescence
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/05/08 06:00
MHDA- 2022/06/09 06:00
PMCR- 2022/04/30
CRDT- 2022/05/07 18:14
PHST- 2022/02/09 00:00 [received]
PHST- 2022/04/25 00:00 [revised]
PHST- 2022/04/26 00:00 [accepted]
PHST- 2022/05/08 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/05/07 18:14 [entrez]
PHST- 2022/04/30 00:00 [pmc-release]
AID - S2213-2317(22)00097-0 [pii]
AID - 102325 [pii]
AID - 10.1016/j.redox.2022.102325 [doi]
PST - ppublish
SO  - Redox Biol. 2022 Jul;53:102325. doi: 10.1016/j.redox.2022.102325. Epub 2022 Apr 
      30.