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

详细信息    查看全文

• 作者：Chencheng Feng¹ ; ^{doctorfgy@163.com} ; Yang Zhang¹ ; ^{65210796@qq.com} ; Minghui Yang¹ ; ^{doc_ymh@163.com} ; Minghong Lan¹ ; ^{fccdoc@me.com} ; Huan Liu¹ ; ^{20016040@163.com} ; Jian Wang¹ ; ^{tonywjxq@aliyun.com} ; Yue Zhou ; ¹ ; ^{happyzhou@vip.163.com} ; Bo Huang ; ¹ ; ^{fmmuhb@126.com}
• 关键词：IVD ; intervertebral disc ; IDD ; intervertebral disc degeneration ; SASP ; senescence-associated secreted phenotype ; NP ; nucleus pulposus ; AF ; annulus fibrosus ; SA-β-Gal ; senescence-associated β-galactosidase ; ECM ; extracellular matrix ; DDR ; DNA damage response ; N-Ac-PGP ; N-acetylated proline-glycine-proline ; RS ; replicative senescence ; Rb ; retinoblastoma protein ; RPX ; Reparixin ; ADAMTS ; a disintegrin and metalloproteinase with thrombospondin motifs ; MMP ; matrix metalloproteinase ; PE ; prolyl endopep
• 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.