PMID- 34172831
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20240229
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 101
IP  - 11
DP  - 2021 Nov
TI  - Th17/IL-17 induces endothelial cell senescence via activation of NF-kappaB/p53/Rb 
      signaling pathway.
PG  - 1418-1426
LID - S0023-6837(22)00281-1 [pii]
LID - 10.1038/s41374-021-00629-y [doi]
AB  - Cellular senescence is a key mechanism of age-related vascular endothelial 
      dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by 
      Th17 cells (a subgroup of helper T cells), which is a key factor in the 
      development of atherosclerosis. However, the effect of IL-17A on the senescence 
      of vascular endothelial cells is still unclear. In this study, we aimed to 
      explore the role of IL-17A on endothelial cell senescence and its signaling 
      pathways associated with senescence. The proportion of Th17 cells in the spleen 
      and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 
      (VCAM-1) in mice of different ages were increased with aging. In vitro 
      experiments showed that proliferation was inhibited, senescent beta-galactosidase 
      and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic 
      endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the 
      NF-kappaB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully 
      inhibited IL-17A-induced expression of senescence-associated proteins. In 
      conclusion, our data reveal a previously unsuspected link between IL-17A and 
      endothelial cell senescence, which was mediated by the NF-kappaB /p53/Rb pathway.
CI  - (c) 2021. The Author(s), under exclusive licence to United States and Canadian 
      Academy of Pathology.
FAU - Zhang, Liang
AU  - Zhang L
AD  - Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical 
      University, Hefei, Anhui, PR China.
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of USTC, 
      Division of Life Science and Medicine, University of Science and Technology of 
      China, Hefei, Anhui, PR China.
FAU - Liu, Manli
AU  - Liu M
AD  - Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical 
      University, Hefei, Anhui, PR China.
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of USTC, 
      Division of Life Science and Medicine, University of Science and Technology of 
      China, Hefei, Anhui, PR China.
FAU - Liu, Wenhua
AU  - Liu W
AD  - Department of Neurology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, PR China.
FAU - Hu, Chaojie
AU  - Hu C
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of USTC, 
      Division of Life Science and Medicine, University of Science and Technology of 
      China, Hefei, Anhui, PR China.
FAU - Li, Hongqi
AU  - Li H
AD  - Geriatric Cardiology Department, Anhui Provincial Hospital, Anhui Medical 
      University, Hefei, Anhui, PR China.
FAU - Deng, Jie
AU  - Deng J
AD  - Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical 
      University, Hefei, Anhui, PR China.
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of USTC, 
      Division of Life Science and Medicine, University of Science and Technology of 
      China, Hefei, Anhui, PR China.
FAU - Cao, Qi
AU  - Cao Q
AD  - The Centre for Transplantation and Renal Research, Westmead Institute for Medical 
      Research, University of Sydney, Sydney, NSW, Australia.
FAU - Wang, Yiping
AU  - Wang Y
AD  - The Centre for Transplantation and Renal Research, Westmead Institute for Medical 
      Research, University of Sydney, Sydney, NSW, Australia.
FAU - Hu, Wei
AU  - Hu W
AD  - Department of Neurology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      Anhui, PR China. andinghu@ustc.edu.cn.
FAU - Li, Qing
AU  - Li Q
AD  - Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical 
      University, Hefei, Anhui, PR China. liqing-2001@163.com.
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of USTC, 
      Division of Life Science and Medicine, University of Science and Technology of 
      China, Hefei, Anhui, PR China. liqing-2001@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210625
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Arteries/physiology
MH  - *Cellular Senescence
MH  - Endothelial Cells/*metabolism
MH  - Interleukin-17/*metabolism
MH  - Interleukin-6/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Retinoblastoma Protein/metabolism
MH  - Signal Transduction
MH  - Th17 Cells/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
MH  - Mice
EDAT- 2021/06/27 06:00
MHDA- 2021/11/16 06:00
CRDT- 2021/06/26 06:08
PHST- 2021/01/30 00:00 [received]
PHST- 2021/06/14 00:00 [accepted]
PHST- 2021/05/29 00:00 [revised]
PHST- 2021/06/27 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/06/26 06:08 [entrez]
AID - S0023-6837(22)00281-1 [pii]
AID - 10.1038/s41374-021-00629-y [doi]
PST - ppublish
SO  - Lab Invest. 2021 Nov;101(11):1418-1426. doi: 10.1038/s41374-021-00629-y. Epub 
      2021 Jun 25.