title: Advanced glycation end products accelerate arteriosclerosis after renal transplantation through the AGE/RAGE/ILK pathway.
abstract: BACKGROUND
  The effects of advanced glycation end products (AGEs) on arteriosclerosis (AS) after kidney transplantation and the molecular mechanisms involved remain unclear.
  
  
  METHODS
  Samples were collected from 30 healthy volunteers and 30 renal transplant recipients (RTRs) to determine the levels of AGEs and to observe both histological changes and α-smooth muscle actin (α-SMA) and osteopontin (OPN) expression. Furthermore, we analyzed α-SMA, OPN and integrin-linked kinase (ILK) in rat vascular smooth muscle cells (VSMCs) that were treated with AGEs and in ILK plasmid transfected rat VSMCs treated with AGEs. Finally, we measured the expression of ILK and the receptor for advanced glycation end (RAGE) products in rat VSMCs treated with AGEs and an anti-RAGE antibody.
  
  
  RESULTS
  Significant differences in the histological changes, serum AGEs, and expression of α-SMA and OPN in arterial walls were noted between healthy volunteers and RTRs. Significant OPN and ILK overexpression and reduced α-SMA expression were detected in a time-dependent manner in rat VSMCs after treatment with AGEs. Similar outcomes were observed regarding the overexpression of ILK, and these results could be prevented via RAGE inhibition.
  
  
  CONCLUSIONS
  AGEs may play a critical role in the formation and progression of AS after renal transplantation by inducing VSMCs-to-osteoblast trans-differentiation through the AGE/RAGE/ILK pathway.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Xuzhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China; Department of Urology, Huai'an First People's Hospital, 6 Beijing West Road, Huai'an, Jiangsu Province 223300, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Suzhou Municipal Hospital, 26 Daoqian Road, Suzhou, Jiangsu Province 215001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Bian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China. Electronic address: Lancetgu@aliyun.com.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China. Electronic address: tanruoyun112@vip.sina.com.
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Tan
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
chemical_list: D017127:Glycation End Products, Advanced; D053495:Osteopontin; D017346:Protein Serine-Threonine Kinases; D000067759:Receptor for Advanced Glycation End Products; D000099200:Scaffold Protein ILK
keywords: AGEs; Arteriosclerosis; ILK; Kidney transplantation; Osteoblast; RAGE; Trans-differentiation; VSMCs