Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity
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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.
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Txnip has a described role in hematopoietic stem cell function, cell-cycle regulation, and stress response.
“This gene was of interest due to its described role in HSC function (34), cell-cycle regulation (35), and stress response (36).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [36]
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Regulation of Hematopoietic Stem Cell Fate and Malignancy
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Inhibition of Osteoclastogenesis by Thioredoxin-Interacting Protein-Derived Peptide (TN13)
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p38α plays differential roles in hematopoietic stem cell activity dependent on aging contexts
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Txnip regulates the Oct4-mediated pluripotency circuitry via metabolic changes upon differentiation
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- Authors
- Jung, H., Kim, D. O., Byun, J.-E., Kim, W. S., Kim, M. J., Song, H. Y., Kim, Y. K., Kang, D.-K., Park, Y.-J., Kim, T.-D., Yoon, S. R., Lee, H. G., Choi, E.-J., Min, S.-H., & Choi, I.
- Affiliations
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Chungbuk National University (KR)
- Scripps Korea Antibody Institute (KR)
- Asan Medical Center (KR)
- Daegu-Gyeongbuk Medical Innovation Foundation (KR)
- Corresponding author
- Jung, Haiyoung
- Choi, Inpyo
- ORCID
- Venue
- Nature Communications
- Published
- 2016-12-08
- Volume
- 7
- Issue
- 1
- Pages
- 13674-13674
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5155146
- OpenAlex
- W2559958687
- Cited by
- 81
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 13 · 2020: 6 · 2019: 11 · 2018: 9 · 2017: 2
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- KRIBB Repository (submittedVersion)
- Funders
- Korea Research Institute of Bioscience and Biotechnology (A121934)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- TXNIP, p38 MAPK, stem cell rejuvenation, cell-penetrating peptides, protein-protein interaction, reactive oxygen species, engraftment
- MeSH terms
- Animals, Carrier Proteins, Female, Hematopoietic Stem Cells, Male, Thioredoxins, Cellular Senescence, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Mice
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