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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

Authors 

Haiyoung JungDong Oh KimJae Eun ByunWon Sam KimMi Jeong KimHae Young SongY K KimDu-Kyeong KangYoung-Jun ParkTae-Don KimSuk Ran YoonHee Gu LeeE J ChoiS H MinIn Pyo Choi

Publisher 

Nature Publishing Group

Issue Date 

2016

Citation 

Nature Communications, vol. 7, no. 0, pp. 13674-13674

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

Link 

http://dx.doi.org/10.1038/ncomms13674

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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