title: Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III.
abstract: Diabetic nephropathy is characterized by progressive mesangial expansion. Although we have reported that circulating oxidized LDL-containing immune complexes (oxLDL-IC) are associated with abnormal levels of albuminuria, the underlying mechanisms have not been investigated. In this study, we have studied the effect of oxLDL-IC on collagen IV expression by mesangial cells. We found that oxLDL-IC markedly stimulated collagen IV expression in a concentration- and time-dependent fashion while oxLDL only had moderate effect. We also found that oxLDL-IC stimulated collagen IV expression by engaging Fc gamma receptor (FcγR) I and III, but not FcγRII, and that p38 MAPK, JNK and PKC pathways were involved in collagen IV expression. Furthermore, we found that oxLDL-IC stimulated FcγRI expression, suggesting a positive feedback mechanism involved in oxLDL-IC-stimulated collagen IV expression. Taken together, this study showed that oxLDL-IC stimulated collagen IV in mesangial cells via FcγRI and FcγRIII, and the expression of FcγRI was increased by oxLDL-IC.
authors: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Souzan A
authors: SA
authors: Abdelsamie
authors: Yanchun
authors: Y
authors: Li
authors: Yan
authors: Y
authors: Huang
authors: Mi-Hye
authors: MH
authors: Lee
authors: Richard L
authors: RL
authors: Klein
authors: Gabriel
authors: G
authors: Virella
authors: Maria F
authors: MF
authors: Lopes-Virella
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000276:immunology; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000276:immunology*; D050527:Mesangial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000936:Antigen-Antibody Complex; D024141:Collagen Type IV; D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; D017452:Receptors, IgG; C099252:oxidized low density lipoprotein; D012313:RNA; D020928:Mitogen-Activated Protein Kinases