PMID- 11961018 OWN - NLM STAT- MEDLINE DCOM- 20021010 LR - 20220419 IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 13 IP - 5 DP - 2002 May TI - Receptor for advanced glycation end products on human synovial fibroblasts: role in the pathogenesis of dialysis-related amyloidosis. PG - 1296-1306 LID - 10.1681/ASN.V1351296 [doi] AB - An important component of amyloid fibrils in dialysis-related amyloidosis (DRA) is beta(2)-microglobulin (beta(2)m) modified with advanced glycation end products (AGE). The amyloid deposits are located principally in joint structures, with adjacent chronic inflammatory reaction characterized by monocyte infiltration. This study examined the interaction of AGE-beta(2)m with human synovial fibroblasts and investigated the proinflammatory effects of that interaction. It was demonstrated that human synovial fibroblasts constitutively expressed the receptor for AGE (RAGE). RAGE expression was detected mainly in synovial intima and was upregulated in DRA synovium. (125)I-AGE-beta(2)m bound to immobilized human synovial fibroblasts in a specific, dose-dependent manner (K(d) of approximately 138.0 nM), and binding was inhibited by anti-RAGE IgG. Incubation of human synovial fibroblasts with AGE-beta(2)m induced degradation of this AGE-modified protein, as well as increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression. The amount of MCP-1 produced by AGE-beta(2)m-stimulated human synovial fibroblasts was sufficient to induce the chemotaxis of monocytes. MCP-1 synthesis resulted from engagement of RAGE, because the increase in MCP-1 synthesis was attenuated by preincubation of human synovial fibroblasts with anti-RAGE IgG. These data provide evidence of RAGE-mediated perturbation of human synoviocytes, which may be involved in the pathogenesis of inflammatory processes associated with DRA. FAU - Hou, Fan Fan AU - Hou FF AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Jiang, Jian Ping AU - Jiang JP AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Guo, Jun Qi AU - Guo JQ AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Wang, Guo Bao AU - Wang GB AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Zhang, Xun AU - Zhang X AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Stern, David M AU - Stern DM AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Schmidt, Ann Marie AU - Schmidt AM AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. FAU - Owen, William F Jr AU - Owen WF Jr AD - *Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Antigens, CD) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, Immunologic) RN - 0 (beta 2-Microglobulin) SB - IM MH - Amyloidosis/*etiology MH - Analysis of Variance MH - Antigens, CD/isolation & purification MH - Blotting, Western MH - Chemokine CCL2/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Fibroblasts/*metabolism MH - Humans MH - Immunohistochemistry MH - Joint Diseases/*etiology MH - Microscopy, Electron MH - Protein Binding MH - RNA, Messenger/metabolism MH - Receptor for Advanced Glycation End Products MH - Receptors, Immunologic/*metabolism MH - Renal Dialysis/*adverse effects MH - Reverse Transcriptase Polymerase Chain Reaction MH - Up-Regulation MH - beta 2-Microglobulin/pharmacology EDAT- 2002/04/19 10:00 MHDA- 2002/10/11 04:00 CRDT- 2002/04/19 10:00 PHST- 2002/04/19 10:00 [pubmed] PHST- 2002/10/11 04:00 [medline] PHST- 2002/04/19 10:00 [entrez] AID - 13/5/1296 [pii] AID - 10.1681/ASN.V1351296 [doi] PST - ppublish SO - J Am Soc Nephrol. 2002 May;13(5):1296-1306. doi: 10.1681/ASN.V1351296.