한빛사논문
- 조회2,484
Abstract
Haiyoung Jung1,2,*, Dong Oh Kim1,2,*, Jae-Eun Byun1,3, Won Sam Kim1,2, Mi Jeong Kim1,2, Hae Young Song1, Young Kwan Kim4, Du-Kyeong Kang5, Young-Jun Park1,2, Tae-Don Kim1,2, Suk Ran Yoon1,2, Hee Gu Lee1,6, Eun-Ji Choi7, Sang-Hyun Min8 & Inpyo Choi1,2
1 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. 2 Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea. 3 Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea. 4 Scripps Korea Antibody Institute, 1 Kangwondaehak-gil, Chuncheon 24341, Republic of Korea. 5 Bioenergy and Biochemical Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea. 6 Department of Biomolecular Science, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea. 7 Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. 8 New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbokro Dong-gu 41061, Daegu, Republic of Korea.
* These authors contributed equally to this work.
Correspondence to Haiyoung Jung or Inpyo Choi.
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.
논문정보
- Research article
- 2016년 12월 (BRIC 등록일 2016-12-14)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
