Open AccessThioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity
Author(s) -
Hye Young Jung,
Dong Oh Kim,
Jaechul Byun,
Won Sam Kim,
Mi Jeong Kim,
Hae Young Song,
Young Kwan Kim,
Du-Kyeong Kang,
Young-Jun Park,
TaeDon Kim,
Suk Ran Yoon,
Hee Gu Lee,
EunJi Choi,
SangHyun Min,
Inpyo Choi
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms13674
Subject(s) - txnip , stem cell , microbiology and biotechnology , haematopoiesis , ageing , biology , p38 mitogen activated protein kinases , protein kinase a , thioredoxin , kinase , biochemistry , oxidative stress , genetics
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.