PMID- 33391511
OWN - NLM
STAT- MEDLINE
DCOM- 20210804
LR  - 20210804
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 11
IP  - 2
DP  - 2021
TI  - Human umbilical cord-derived mesenchymal stem cell therapy ameliorates lupus 
      through increasing CD4+ T cell senescence via MiR-199a-5p/Sirt1/p53 axis.
PG  - 893-905
LID - 10.7150/thno.48080 [doi]
AB  - Rationale: Although human umbilical cord-derived mesenchymal stem cells 
      (hUC-MSCs) transplantation has been proved to be an effective therapeutic 
      approach to treat systemic lupus erythematosus (SLE), the detailed underlying 
      mechanisms are not fully understood. Transferring miRNAs is one mean by which 
      MSCs communicate with surrounding cells. Sirt1 is a NAD-dependent deacetylase 
      that protects against cell senescence by deacetylating p53. Here we aimed to 
      explore whether hUC-MSCs affected senescence of splenic CD4+ T cells through 
      regulating Sirt1/p53 via miRNA in the MRL/lpr lupus mouse model. Methods: The 
      effects of hUC-MSCs on lupus syndrome and senescence pathways in MRL/lpr mice in 
      vivo and in vitro were determined. The functional roles of miR-199a-5p in splenic 
      CD4+ T cell senescence were studied by miRNA mimic or inhibitor in vitro. MRL/lpr 
      mice were injected with miR-199a-5p agomir to evaluate the effects of miR-199a-5p 
      on splenic CD4+ T cell senescence and disease in vivo.Results: We showed that 
      hUC-MSCs transplantation ameliorated lupus symptoms and increased senescence of 
      splenic CD4+ T cells through Sirt1/p53 signaling via miR-199a-5p in MRL/lpr mice. 
      Moreover, systemic delivery of miR-199a-5p in MRL/lpr mice increased splenic CD4+ 
      T-cell senescence, mimicking the therapeutic effects of transplanted hUC-MSCs. 
      Conclusions: We have identified miR-199a-5p as one of the mechanisms employed by 
      hUC-MSCs to alleviate lupus disease associated pathologies in MRL/lpr mice, which 
      is attributable for promoting splenic CD4+ T cell senescence through Sirt1/p53 
      pathway.
CI  - (c) The author(s).
FAU - Cheng, Tao
AU  - Cheng T
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Medical School of Nanjing University, Nanjing, 210008 China.
FAU - Ding, Shuai
AU  - Ding S
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Medical School of Nanjing University, Nanjing, 210008 China.
FAU - Liu, Shanshan
AU  - Liu S
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Medical School of Nanjing University, Nanjing, 210008 China.
FAU - Li, Yan
AU  - Li Y
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and 
      Biomedicine Innovation Center, Model Animal Research Center of Nanjing 
      University, Nanjing, 210061 China.
FAU - Sun, Lingyun
AU  - Sun L
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Medical School of Nanjing University, Nanjing, 210008 China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210101
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn199 microRNA, mouse)
RN  - 0 (Trp53 protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - *Cellular Senescence
MH  - Female
MH  - Lupus Erythematosus, Systemic/immunology/metabolism/pathology/*therapy
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mice, Inbred MRL lpr
MH  - MicroRNAs/*genetics
MH  - Sirtuin 1/genetics/*metabolism
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - Umbilical Cord/cytology
PMC - PMC7738872
OTO - NOTNLM
OT  - Lupus
OT  - Mesenchymal stem cells
OT  - Senescence
OT  - Sirt1/p53
OT  - miR-199a-5p
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/01/05 06:00
MHDA- 2021/08/05 06:00
PMCR- 2021/01/01
CRDT- 2021/01/04 05:28
PHST- 2020/05/11 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2021/01/04 05:28 [entrez]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/08/05 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - thnov11p0893 [pii]
AID - 10.7150/thno.48080 [doi]
PST - epublish
SO  - Theranostics. 2021 Jan 1;11(2):893-905. doi: 10.7150/thno.48080. eCollection 
      2021.