Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro
Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro
复制标题
DOI：
10.1046/j.1523-1755.2001.00573.x
复制
发表时间：
2001-03-01
影响因子：
19.6
通讯作者：
Shankland, SJ
中科院分区：
文献类型：
--
作者：
Couser, WG;Pippin, JW;Shankland, SJ
背景膜攻击复合物 C5b-9 会导致多种形式的免疫介导的肾小球疾病损伤，其特征是系膜细胞 (MC) 增殖，抑制 C5b-9 可降低体内 MC 增殖。补体膜攻击复合物 (C5b-9) 的亚溶解量的膜插入可有效刺激细胞活化和产生各种细胞因子、生长因子、氧化剂、基质成分和其他肾炎分子。在体内，MC 对 C5b-9 介导的损伤的常见反应是细胞增殖，这是与基质扩张和硬化密切相关的事件。在这项研究中，我们测试了 C5b-9 也可能作为 MC 的有丝分裂刺激物的假设。方法。将体外大鼠 MC 暴露于抗 Thy1 抗体和 2% 正常 PVG 血清（补体来源）以诱导亚裂解性 C5b-9 攻击，并测量 DNA 合成和细胞数量。将对照 MC 暴露于抗体和 C6 缺陷型 PVG 血清。结果。 C5b-9 诱导的 MC 损伤足以诱导 DNA 合成。此外，C5b-9 增强了血小板衍生生长因子 (PDGF) 和 5% 胎牛血清诱导的 DNA 合成。使用超氧化物歧化酶和过氧化氢酶抑制活性氧 (ROS) 可以减少 C5b-9 诱导的 DNA 合成，但不能通过中和有丝分裂生长因子 PDGF 和碱性成纤维细胞生长因子 (bFGF) 来减少。结论。这项研究表明，C5b-9 可以直接增加培养的 MC 中的 DNA 合成，这部分是通过 ROS 的释放介导的，并且 C5b-9 还可以增强其他已知有丝分裂原在 MC 中诱导的 DNA 合成。
Background The membrane attack complex C5b-9 causes injury in many forms of immune-mediated glomerular diseases characterized by mesangial cell (MC) proliferation and inhibiting C5b-9 decreases MC proliferation in vivo. Membrane insertion of sublytic quantities of the membrane attack complex of complement (C5b-9) is a potent stimulus for cell activation and the production of a variety of cytokines, growth factors, oxidants, matrix components, and other nephritogenic molecules. In vivo, a common response of MC to C5b-9-mediated injury is cell proliferation, an event closely linked to matrix expansion and sclerosis. In this study, we tested the hypothesis that C5b-9 might also serve as a mitogenic stimulus for MCs.Methods. Rat MCs in vitro were exposed anti-Thy1 antibody and 2% normal PVG serum (a complement source) to induce sublytic C5b-9 attack and DNA synthesis and cell number were measured. Control MCs were exposed to antibody and C6-deficient PVG serum.Results. Sublytic C5b-9-induced injury to MCs is sufficient to induce DNA synthesis. Furthermore, C5b-9 augmented DNA synthesis induced by platelet-derived growth factor (PDGF) and 5% fetal calf serum. C5b-9-induced DNA synthesis was reduced by inhibiting reactive oxygen species (ROS) with superoxide dismutase and catalase, but not by neutralizing the mitogenic growth factors PDGF and basic fibroblast growth factor (bFGF).Conclusions. This study demonstrates that C5b-9 may directly increase DNA synthesis in cultured MCs, which are mediated in part by the release of ROS, and that C5b-9 also augments DNA synthesis induced in MCs by other known mitogens.