The matrikine N-acetylated proline-glycine-proline induces premature senescence of nucleus pulposus cells via CXCR1-dependent ROS accumulation and DNA damage and reinforces the destructive effect of these cells on homeostasis of intervertebral discs
刊名:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
出版年:2017
出版时间:January 2017
年:2017
卷:1863
期:1
页码:220-230
全文大小:2863 K
卷排序:1863
文摘
N-Ac-PGP induces premature senescence of NP cells through CXCR1-dependent DNA damage and ROS production which activates the p53-p21-Rb and p16-Rb pathways. The glutathione (GSH) system and thioredoxin (Trx) system in NP cells are reduced by N-Ac-PGP. N-Ac-PGP regulates the senescence-associated secretory phenotype (SASP) of NP cells by inducing the expression of matrix proteases, chemokines and cytokines. N-Ac-PGP enhances the in vivo destructive effects of senescent NP cells on structural and functional maintenance of IVD. N-Ac-PGP is a new potential therapeutic target of disc cell senescence and IDD.