title: Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting TGF-β1-p38 MAPK pathway.
abstract: OBJECTIVE
  Beta 2 glycoprotein I (β2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. β2GPI can be reduced by thioredoxin-1, resulting in the reduced state of β2GPI. The possible protective effects of β2GPI and reduced β2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that β2GPI and reduced β2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC).
  
  
  METHODS
  The STZ-induced Balb/c mice and HG exposed RMCs were administrated with β2-GPI and reduced β2-GPI at different time and concentrations gradient respectively. The changes of glomerular structure and expression of collagen IV, TGF-β1, p38 MAPK and phospho-p38 MAPK in renal cortical and mesangial cells were observed by immunohistochemical techniques, quantitative real-time PCR and western blot with or without the treatment of β2-GPI and reduced β2-GPI.
  
  
  RESULTS
  β2GPI and reduced β2GPI improved early clinical and pathological changes of DN in STZ-diabetic mice. Treatment with β2GPI and reduced β2GPI in the STZ-diabetic mice and HG exposed RMCs resulted in decrease expression levels of TGF-β1 and collagen IV, with concomitant decrease in phospho-p38 MAPK expression.
  
  
  CONCLUSIONS
  β2GPI and reduced β2GPI improved renal structural damage and kidney function. The renoprotective and antifibrosis effects of β2GPI and reduced β2GPI on DN were closely associated with suppressing the activation of the TGF-β1-p38 MAPK pathway.
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University Tianjin 300070, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University Tianjin 300070, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Chen
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University Tianjin 300070, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University Tianjin 300070, China.
authors.forename: De-Min
authors.initials: DM
authors.lastname: Yu
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University Tianjin 300070, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004789:Enzyme Activation; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D024141:Collagen Type IV; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D053482:beta 2-Glycoprotein I; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Beta 2 glycoprotein I; TGF-β1; diabetic nephropathy