title: SDF-1α/CXCR4 axis is involved in glucose-potentiated proliferation and chemotaxis in rat vascular smooth muscle cells.
abstract: Excessive proliferation of vascular smooth muscle cells (VSMCs), which migrate from the tunica media to the subendothelial region, is one of the primary lesions involved in atherogenesis in diabetes. Here, we investigated whether high glucose potentiated the proliferation and chemotaxis of VSMCs by activating SDF-1α/CXCR4/PI-3K/Akt signalling. The expression of SDF-1α, CXCR4 and PCNA was up-regulated in tunica media of thoracic aortas by streptozotocin-induced hyperglycaemic Sprague-Dawley rats. Exposure of primary VSMCs to high glucose (25 mM) led to the up-regulated expression of SDF-1α and CXCR4, activated PI-3K/Akt signalling, and consequently promoted the proliferation and chemotaxis of VSMCs. Interestingly, the administration of SDF-1 siRNA or neutralizing antibody against SDF-1α abolished high glucose-induced up-regulation of CXCR4. Moreover, pretreatment with SDF-1α neutralizing antibody, CXCR4 specific inhibitor (AMD3100) or PI-3K inhibitor (LY294002) attenuated the high glucose-potentiated proliferation and chemotaxis in VSMCs. These results suggested that high glucose activated the SDF-1α/CXCR4/PI-3K/Akt signalling pathway in VSMCs in an autocrine manner, which enhanced the proliferation and chemotaxis of VSMCs.
authors.affiliation: Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jie
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Junli
authors.initials: J
authors.lastname: Guo
authors.forename: Dong
authors.initials: D
authors.lastname: Kuang
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhu
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.forename: Qilin
authors.initials: Q
authors.lastname: Ao
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000473:pathology* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose