Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity = Thioredoxin-interacting protein에의한 조혈줄기세포의 노화 및 회춘 조절

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Title
Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity = Thioredoxin-interacting protein에의한 조혈줄기세포의 노화 및 회춘 조절
Author(s)
Haiyoung Jung; Dong Oh Kim; Jae Eun Byun; Won Sam Kim; Mi Jeong Kim; Hae Young Song; Y K Kim; Du-Kyeong Kang; Young-Jun ParkTae-Don KimSuk Ran YoonHee Gu Lee; E J Choi; S H Min; In Pyo Choi
Bibliographic Citation
Nature Communications, vol. 7, pp. 13674-13674
Publication Year
2016
Abstract
Ageing is a natural process in living organisms throughout their lifetime, and most elderly people suffer from ageing-associated diseases. One suggested way to tackle such diseases is to rejuvenate stem cells, which also undergo ageing. Here we report that the thioredoxin-interacting protein (TXNIP)-p38 mitogen-activated protein kinase (p38) axis regulates the ageing of haematopoietic stem cells (HSCs), by causing a higher frequency of long-term HSCs, lineage skewing, a decrease in engraftment, an increase in reactive oxygen species and loss of Cdc42 polarity. TXNIP inhibits p38 activity via direct interaction in HSCs. Furthermore, cell-penetrating peptide (CPP)-conjugated peptide derived from the TXNIP-p38 interaction motif inhibits p38 activity via this docking interaction. This peptide dramatically rejuvenates aged HSCs in vitro and in vivo. Our findings suggest that the TXNIP-p38 axis acts as a regulatory mechanism in HSC ageing and indicate the potent therapeutic potential of using CPP-conjugated peptide to rejuvenate aged HSCs.
ISSN
2041-1723
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/ncomms13674
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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