The Pro-Inflammatory Function Research Of Angiopoietin-Like Protein 7

Inflammation is a pivotal physiological and pathological process associating closely with human and other animals health. It is well known that inflammation plays a critical role in cancer, diabetes, neurodegenerative disease and cardiovascular disease, and is has been considered as the inducer and promoter of this diseases.In resent years, researches focusing on cardiovascular disease revealed that many cytokines, especially the adipocytokines(such as TNFα and Resistin), could elicit the inflammation and participate in the inflammatory process. The angiopoietin-like proteins(Angptls) is a family of secrete glycoproteins. Angptl2 and Angptl4 have been reported for their inflammatory functions recently. Angptl7 is a newly cloned member of Angptls. A number of evidences have been presented recently for the Angptl7 physiological and pathological roles in corneal morphogenesis, angiogenesis, glaucoma and cancer. To date, whether the Angptl7 exhibits the inflammatory property is still unknown.By transfection, RT-PCR, western blot, flow cytometry and FITC-dextran phagocytosis, we studied the relations between Angptl7 and inflammation, and we found:(1) Angptl7 significantly promoted the inflammation-related genes P65, COX-2, iNOS, IL-1β, TNFα, IL-6, IL-10 and TGF-β1 expression and elevated the inflammation-related cytokines TNFα, IL-1β, IL-10 and TGF- β1 secretion;(2) Angptl7 promoted the SR-A and CD36 expression and enhanced the phagocytosis;(3) Angptl7 promoted the CCR2, ITGB1 and ITGB7 expression and strengthened the migration;(4) Angptl7 down-regulated the TGF-β pathway genes TGFBR2, SMAD2 and SMAD3 and the DEX pathway genes GRα, GRβ and GLIZ expression, and antagonized the anti-inflammatory function of TGF-β and DEX;(5) Angptl7 decreased the CDK2 and CDK4 expression and inhibited the proliferation;(6) Angptl7 increased the NF-κB pathway key factor p65 and P38 MAPK pathway key factor p38 protein amounts and phosphorylation levels, and promoted the inflammatory function through P38 MAPK pathway;(7) intraperitoneal injections of recombinant TNFα in a mouse model of peripheral inflammation induced Angptl7 expression in eye.Thus, we proved Angptl7 is a pro-inflammatory cytokine that promotes RAW264.7 cells inflammatory functions via P38 MAPK signaling pathway, reveling a potential therapeutic target for treatment of glaucoma and cancer.