title: The Annexin a2 Promotes Development in Arthritis through Neovascularization by Amplification Hedgehog Pathway.
abstract: The neovascularization network of pannus formation plays a crucial role in the development of rheumatoid arthritis (RA). Annexin a2 (Axna2) is an important mediating agent that induces angiogenesis in vascular diseases. The correlation between Axna2 and pannus formation has not been studied. Here, we provided evidence that compared to osteoarthritis (OA) patients and healthy people, the expression of Axna2 and Axna2 receptor (Axna2R) were up-regulated in patients with RA. Joint swelling, inflammation and neovascularization were increased significantly in mice with collagen-induced arthritis (CIA) that were exogenously added Axna2. Cell experiments showed that Axna2 promoted HUVEC proliferation by binding Axna2R, and could activate Hedgehog (HH) signaling and up-regulate the expression of Ihh and Gli. Besides, expression of Ihh, Patched (Ptc), Smoothened (Smo) and Gli and matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), angiogenic growth factor of HH signaling downstream, were down-regulated after inhibition of expression Axna2R on HUVEC. Together, our research definitely observed that over-expression of Axna2 could promote the development of CIA, especially during the process of pannus formation for the first time. Meanwhile, Axna2 depended on combining Axna2R to activate and enlarge HH signaling and the expression of its downstream VEGF, Ang-2 and MMP-2 to promote HUVEC proliferation, and eventually caused to angiogenesis. Therefore, the role of Axna2 is instructive for understanding the development of RA, suppress the effect of Axna2 might provide a new potential measure for treatment of RA.
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hongdie
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Dejing
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Binghua
authors.initials: B
authors.lastname: Jiao
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
authors.forename: Lianghua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Kaihui
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D053823:Hedgehog Proteins / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D053823:Hedgehog Proteins; C509246:IHH protein, human; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C514061:ihh protein, mouse; C467480:vascular endothelial growth factor A, mouse; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse