Tong Wang1, Si-Si Chen1, Rui Chen1, De-Min Yu1, Pei Yu1. 1. 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.
Abstract
PURPOSE: 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.
PURPOSE: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 diabeticmice 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-diabeticmice. Treatment with β2GPI and reduced β2GPI in the STZ-diabeticmice 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: Yiannis Ioannou; Jing-Yun Zhang; Miao Qi; Lu Gao; Jian Cheng Qi; De-Min Yu; Herman Lau; Allan D Sturgess; Panayiotis G Vlachoyiannopoulos; Haralampos M Moutsopoulos; Anisur Rahman; Charis Pericleous; Tatsuya Atsumi; Takao Koike; Stephane Heritier; Bill Giannakopoulos; Steven A Krilis Journal: Arthritis Rheum Date: 2011-09