Budde K, Neumayer H H, Salant D J, Cybulsky A V, Coleman D L, Sterzel R B
Department of Internal Medicine-Nephrology, Universitätsklinikum Charité, Humboldt University, Berlin, Germany.
Kidney Int. 1997 Sep;52(3):733-41. doi: 10.1038/ki.1997.389.
Glomerular epithelial cells (GEC) and mesangial cells (MC) are both involved in glomerular diseases. To elucidate potential interactions between these glomerular cell types, we examined whether products of GEC affect the proliferative activity of MC. We found that cultured rat GEC secrete soluble factors into the supernate (GEC-CM) that induce proliferation of quiescent rat MC. The mitogenic activity was trypsin sensitive and partially heat-labile. Biochemical analysis of GEC-CM by gel filtration HPLC, reverse phase HPLC, and isoelectric focusing revealed at least three mitogenic fractions as well as inhibitory activity present in GEC-CM. Competitive binding assays with 125I-labeled PDGF did not show significant amounts of PDGF in GEC-CM. The biochemical features of the GEC-derived MC growth factors are distinct from IL-6, PDGF, bFGF, and endothelin, previously described GEC-derived MC growth factors. Additionally, significant contributions of known growth factors such as IL-1, IL-2, IL-3, IL-4, IL-5, TNF alpha, TGF beta, and GM-CSF are unlikely. The results indicate that GEC produce several biochemically-distinct MC growth regulators. While these epithelial cell-derived mitogens for MC require further characterization, they may play an important role in the regulation of MC replication, such as during embryogenesis and glomerular disease.
肾小球上皮细胞（GEC）和系膜细胞（MC）均参与肾小球疾病。为阐明这些肾小球细胞类型之间的潜在相互作用，我们研究了GEC的产物是否影响MC的增殖活性。我们发现，培养的大鼠GEC向培养液上清中分泌可溶性因子（GEC-CM），该因子可诱导静止的大鼠MC增殖。促有丝分裂活性对胰蛋白酶敏感且部分对热不稳定。通过凝胶过滤HPLC、反相HPLC和等电聚焦对GEC-CM进行生化分析，结果显示GEC-CM中至少存在三种促有丝分裂组分以及抑制活性。用125I标记的血小板衍生生长因子（PDGF）进行的竞争性结合试验表明，GEC-CM中不存在大量的PDGF。GEC来源的MC生长因子的生化特征与先前描述的GEC来源的MC生长因子白细胞介素-6（IL-6）、PDGF、碱性成纤维细胞生长因子（bFGF）和内皮素不同。此外，已知生长因子如IL-1、IL-2、IL-3、IL-4、IL-5、肿瘤坏死因子α（TNFα）、转化生长因子β（TGFβ）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的显著作用也不太可能。结果表明，GEC产生几种生化特性不同的MC生长调节因子。虽然这些上皮细胞来源的MC有丝分裂原需要进一步表征，但它们可能在MC复制的调节中发挥重要作用，例如在胚胎发生和肾小球疾病期间。
