Composition comprising peptide derived from thioredoxin-interacting protein or polynucleotide encoding the peptide for rejuvenation of stem cell

• Main Authors: CHOI, IN PYO, BYUN, JAE EUN, JUNG, HAI YOUNG, KIM, DONG OH, KIM, MI JEONG
• Format: Patent
• Language: English; Korean
• Published: 30.03.2018
• Subjects: CHEMISTRY; FOODS OR FOODSTUFFS; FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BYSUBCLASSES A23B - A23J; HUMAN NECESSITIES; HYGIENE; INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLICBEVERAGES; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL; SPECIFIC USE OF COSMETICS OR SIMILAR TOILETPREPARATIONS; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OFNUTRITIVE QUALITIES, PHYSICAL TREATMENT; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES

The present invention relates to a pharmaceutical composition for reverse aging of aged stem cells, wherein the pharmaceutical composition contains a peptide derived from thioredoxin-interacting protein (TXNIP) or a polynucleotide encoding the same as an active ingredient. It has been confirmed that the peptide derived from TXNIP increases engraftment of aged hematopoietic stem cells (HSC), deceases a serial biasing tendency, decreases a long-term HSC (LT-HSC) ratio, and suppresses p38 and ROS in a mouse in which competitive transplantation is performed by using aged HSCs compared to a control group which is not treated with a peptide. Thus, it has been confirmed that the characteristics of aged HSCs are suppressed, and it has been confirmed that administration of a peptide derived from TXNIP increases the proliferation of leukocytes of an aged mouse to a level of a young mouse in an acute leucopenia model. In addition, it has been confirmed that the peptide derived from TXNIP recovers an extremity phenomenon of Cdc42 in aged HSCs, decreases expression of p16, p19, p21, and Wnt5a which are aging-related genes, and increases homing of HSCs. Accordingly, the peptide derived from TXNIP of the present invention can be useful as a composition for reverse aging of HSCs. 본 발명은 티오레독신 결합단백질(Thioredoxin-interacting protein, TXNIP) 유래 펩타이드 또는 이를 암호화 하는 폴리뉴클레오타이드를 유효성분으로 함유하는 줄기세포의 역노화용 약학적 조성물에 관한 것으로, TXNIP 유래 펩타이드는 노령의 조혈모세포(HSC)를 이용하여 경쟁적 이식을 실시한 생쥐에서 펩타이드를 처리하지 않은 대조군에 비하여 노령 HSC의 생착을 증가시키고, 계열편향 경향을 감소시켰으며, LT-HSC(long-term HSC) 비율을 감소시키고, p38 및 ROS를 억제하는 것을 확인함으로써 노화된 HSC의 특징이 억제되는 것을 확인하였고, TXNIP 유래 펩타이드의 투여가 급성 백혈구 감소증 모델에서 노령 생쥐의 백혈구 증식을 어린 생쥐 수준으로 증진시키는 것을 확인하였으며, 또한 TXNIP 유래 펩타이드가 노령의 HSC에서 Cdc42의 극화 현상을 회복 시키고, 노화관련 유전자인 p16, p19, p21 및 Wnt5a의 발현을 감소시키며, HSC의 귀소(homing)를 증가시키는 것을 확인함으로써, 본 발명의 TXNIP 유래 펩타이드는 조혈줄기세포의 역노화용 조성물로써 유용하게 사용될 수 있다.