title: Heparanase-driven inflammation from the AGEs-stimulated macrophages changes the functions of glomerular endothelial cells.
abstract: OBJECTIVE
  Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs).
  
  
  METHODS
  The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages. The expression of the adherence molecules and tight junction proteins in GEnCs were assessed by western. The adherence of mononuclear cells to GEnCs were observed by HE staining and transendothelial FITC-BSA were tested for the permeability of GEnCs.
  
  
  RESULTS
  HPA siRNA and heparanase inhibitor sulodexide could attenuate the increasing inflammatory factors (TNF-α and IL-1β) in AGEs-stimulated macrophages. NF-κB inhibitor PDTC could also decrease the augmented inflammation cytokines through inhibiting the activation of the NF-κB pathway induced by AGEs. The phosphorylation of NF-κB signaling pathway could be also attenuated by HPA siRNA and sulodexide, the same to the receptor of AGEs RAGE. When the macrophage-conditioned culture medium were added to the glomerular endothelial cells, we found HPA siRNA and sulodexide groups could decrease the increasing adherence and permeability of GEnCs induced by AGEs.
  
  
  CONCLUSIONS
  Heparanase increases the inflammation in AGEs-stimulated macrophages through activating the RAGE-NF-κB pathway. Heparanase driven inflammation from AGEs-stimulated macrophages increases the adherence of GEnCs and augments the permeability of GEnCs.
authors.affiliation: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Qiaojing
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China; Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China. Electronic address: njyphd2008@163.com.
authors.forename: Jianying
authors.initials: J
authors.lastname: Niu
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D017127:Glycation End Products, Advanced; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000099175:Heparanase; C007858:glucuronyl glucosamine glycan sulfate
keywords: Advanced glycation end products; Glomerular endothelial cell; Heparanase; Inflammatory factor; Permeability