PMID- 10916091 OWN - NLM STAT- MEDLINE DCOM- 20000907 LR - 20221207 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 58 IP - 2 DP - 2000 Aug TI - Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. PG - 684-90 AB - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a specific chemokine to recruit and activate monocytes from the circulation to inflammatory site. In diabetic nephropathy, similar to other glomerulonephropathies, infiltration and activation of monocytes/macrophages in glomerulus have been implicated in the development of glomerular injury. The aim of the present study was to examine a possible relationship of MCP-1 with diabetic nephropathy and to investigate the role of glycated albumin (Gly-Alb) as well as high concentration of glucose (HG) on MCP-1 production by cultured human mesangial cells. METHODS: MCP-1 in serum or urine and urinary albumin (Alb) as well as several clinical parameters such as plasma glucose, serum Gly-Alb, and hemoglobin A1c (HbA1c) were measured after overnight fasting in 16 control subjects and 54 diabetic patients. The relationships between the levels of urinary Alb and urinary or serum MCP-1 and also between the values of respective clinical parameter and urinary MCP-1 levels were analyzed. Next, using cultured human mesangial cells, we investigated the role of Gly-Alb and/or HG on the gene and protein expression of MCP-1. RESULTS: Urinary levels (ng/g creatinine), but not serum levels, of MCP-1 increased in accordance with the extent of albuminuria. In all subjects, there were significant correlations between the urinary levels of Alb and MCP-1 (r = 0.746, P < 0.0001) and between the levels of serum Gly-Alb and urinary MCP-1 (r = 0.475, P < 0.0001). In cultured human mesangial cells, the gene and protein expression of MCP-1 was dose and time dependently up-regulated by Gly-Alb. HG slightly but significantly stimulated MCP-1 expression. The combination of Gly-Alb and HG showed the greatest stimulation in more than an additive manner on MCP-1 production. CONCLUSIONS: This study suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy. FAU - Banba, N AU - Banba N AD - Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Tochigi, Japan. FAU - Nakamura, T AU - Nakamura T FAU - Matsumura, M AU - Matsumura M FAU - Kuroda, H AU - Kuroda H FAU - Hattori, Y AU - Hattori Y FAU - Kasai, K AU - Kasai K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Blood Glucose) RN - 0 (Chemokine CCL2) RN - 0 (Glycation End Products, Advanced) RN - 0 (Serum Albumin) RN - 0 (Glycated Serum Albumin) SB - IM MH - Adult MH - Albuminuria/blood/immunology/urine MH - Blood Glucose MH - Cells, Cultured MH - Chemokine CCL2/*blood/metabolism/*urine MH - Diabetes Mellitus, Type 1/blood/immunology/urine MH - Diabetes Mellitus, Type 2/blood/immunology/urine MH - Diabetic Nephropathies/blood/*immunology/urine MH - Female MH - Glomerular Mesangium/cytology MH - Glycation End Products, Advanced MH - Humans MH - Hyperglycemia/blood/immunology/urine MH - Male MH - Middle Aged MH - *Serum Albumin MH - Glycated Serum Albumin EDAT- 2000/08/01 11:00 MHDA- 2000/09/09 11:01 CRDT- 2000/08/01 11:00 PHST- 2000/08/01 11:00 [pubmed] PHST- 2000/09/09 11:01 [medline] PHST- 2000/08/01 11:00 [entrez] AID - S0085-2538(15)47148-0 [pii] AID - 10.1046/j.1523-1755.2000.00214.x [doi] PST - ppublish SO - Kidney Int. 2000 Aug;58(2):684-90. doi: 10.1046/j.1523-1755.2000.00214.x.