氧化型 LDL 免疫复合物通过 Fcγ 受体 I 和 III 刺激系膜细胞胶原 IV 的产生。
Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III.
机构信息
Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
出版信息
Clin Immunol. 2011 Jun;139(3):258-66. doi: 10.1016/j.clim.2011.01.016. Epub 2011 Feb 10.
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.
摘要
糖尿病肾病的特征是进行性系膜扩张。虽然我们已经报告了循环氧化 LDL 包含的免疫复合物（oxLDL-IC）与异常白蛋白尿水平有关，但尚未研究其潜在机制。在这项研究中，我们研究了 oxLDL-IC 对系膜细胞胶原 IV 表达的影响。我们发现 oxLDL-IC 以浓度和时间依赖的方式显著刺激胶原 IV 表达，而 oxLDL 只有适度的作用。我们还发现 oxLDL-IC 通过结合 Fcγ 受体（FcγR）I 和 III 刺激胶原 IV 表达，而不是 FcγRII，并且 p38 MAPK、JNK 和 PKC 途径参与胶原 IV 表达。此外，我们发现 oxLDL-IC 刺激 FcγRI 表达，提示 oxLDL-IC 刺激胶原 IV 表达涉及正反馈机制。总之，这项研究表明 oxLDL-IC 通过 FcγRI 和 FcγRIII 刺激系膜细胞胶原 IV，oxLDL-IC 增加了 FcγRI 的表达。
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