Frank J, Engler-Blum G, Rodemann H P, Müller G A
Department 3, Medical University Clinics, University of Tübingen, FRG.
Exp Nephrol. 1993 Jan-Feb;1(1):26-35.
The pathogenesis of renal interstitial fibrosis is not fully understood at present. As renal interstitial fibrosis occurs mainly in association with interstitial cell infiltrates, several cytokines, e.g. PDGF, TGF-beta, IL-6, are thought to play a major role in the induction and progression of renal interstitial fibrosis. In order to prove whether renal tubular epithelial cells produce cytokines which are known to modulate renal interstitial fibroblasts, RNA was isolated from human renal tubular epithelial cells and from human renal fibroblasts. The expression of specific cytokines and growth factors was analysed by Northern blot analysis using cDNA probes for IL-1 alpha, IL-1 beta, IL-6, INF-gamma, TNF-alpha, a-FGF, b-FGF, GM-CSF, PDGF-B and oligonucleotides for IL-2 and TGF-beta 1. In renal tubular epithelial cells from normal and diseased kidneys, mRNA transcripts for PDGF-B, IL-6 and GM-CSF could be detected. Quantitative analysis of the mRNA transcripts of the cytokines expressed revealed consistently higher amounts of GM-CSF and PDGF-B mRNA in tubular epithelial cells from diseased in comparison to normal kidneys. Furthermore, higher amounts of GM-CSF and PDGF-B mRNA transcripts were detected in tubular epithelial cells derived from kidneys with interstitial fibrosis as compared to tubular epithelial cells from diseased but nonfibrotic kidneys. Renal fibroblasts from normal and fibrotic kidneys showed a weak signal for IL-6, but PDGF-B and GM-CSF were not expressed in these cells. By means of colony assays, using human bone marrow cells in the presence or absence of neutralizing antibodies, the release of biologically active colony-stimulating factors GM-CSF and M-CSF by renal tubular epithelial cells from normal and diseased kidneys could be demonstrated. The present results probably indicate interactions between renal tubular epithelial cells and renal fibroblasts in the progression of renal diseases.
目前，肾间质纤维化的发病机制尚未完全明确。由于肾间质纤维化主要与间质细胞浸润相关，因此，几种细胞因子，如血小板衍生生长因子（PDGF）、转化生长因子-β（TGF-β）、白细胞介素-6（IL-6），被认为在肾间质纤维化的诱导和进展中起主要作用。为了证实肾小管上皮细胞是否产生已知可调节肾间质成纤维细胞的细胞因子，从人肾小管上皮细胞和人肾成纤维细胞中分离出RNA。使用针对IL-1α、IL-1β、IL-6、干扰素-γ（INF-γ）、肿瘤坏死因子-α（TNF-α）、α-成纤维细胞生长因子（a-FGF）、b-成纤维细胞生长因子（b-FGF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、血小板衍生生长因子-B（PDGF-B）的cDNA探针以及针对IL-2和转化生长因子-β1（TGF-β1）的寡核苷酸，通过Northern印迹分析来检测特定细胞因子和生长因子的表达。在正常和患病肾脏的肾小管上皮细胞中，可检测到PDGF-B、IL-6和GM-CSF的mRNA转录本。对所表达细胞因子的mRNA转录本进行定量分析发现，与正常肾脏相比，患病肾脏的肾小管上皮细胞中GM-CSF和PDGF-B mRNA的含量始终更高。此外，与患病但未发生纤维化的肾脏的肾小管上皮细胞相比，在间质纤维化肾脏的肾小管上皮细胞中检测到更高含量的GM-CSF和PDGF-B mRNA转录本。正常和纤维化肾脏的肾成纤维细胞对IL-6显示出微弱信号，但这些细胞中未表达PDGF-B和GM-CSF。通过集落测定法，在有或无中和抗体存在的情况下使用人骨髓细胞，可证明正常和患病肾脏的肾小管上皮细胞释放具有生物活性的集落刺激因子GM-CSF和巨噬细胞集落刺激因子（M-CSF）。目前的结果可能表明在肾脏疾病进展过程中肾小管上皮细胞与肾成纤维细胞之间存在相互作用。
