Sommer M, Eismann U, Deuther-Conrad W, Wendt T, Mohorn T, Fünfstück R, Stein G
Department of Internal Medicine IV, University of Jena, Germany.
Nephron. 2000 Jan;84(1):49-57. doi: 10.1159/000045538.
The development of renal interstitial fibrosis (RIF) is related to the expression and excretion of cytokines and growth factors. Thus, we investigated the time course of mRNA expression of cytokines known as causative factors in a model of RIF in rats before and on day 10 after unilateral ureteral obstruction (UUO), when first signs of fibrosis were visible, as well as during progressive RIF. UUO causes a fivefold increase in mRNA expression of monocyte chemoattractant protein 1 15 days after surgery as compared with contralateral kidneys. The level remains elevated about three-fold up to day 25. The mRNA of the fibrogenic cytokine transforming growth factor beta 1 (TGF-beta1) is increased two- to threefold during the time course, whereas the mRNAs of platelet-derived growth factor B chain (PDGF-B) and its receptor beta (PDGF-Rbeta) increase after UUO, reaching their maxima on days 10-15. PDGF-B mRNA increase up to day 15, marking the onset of fibrosis, and decreases thereafter, whereas the expression of the PDGF-Rbeta mRNA remains elevated more than threefold over the entire study period. Incubation of cultured renal fibroblasts with TGF-beta1 and/or PDGF-B suggests that their specific action on cell growth and proliferation is maintained even when they are used in combination. The sustained elevation of TGF-beta1 and PDGF-B/PDGF-Rbeta mRNA levels confirms the assumption of a particular involvement of these cytokines in the pathogenesis of RIF. The mRNA expression of the gap junctional protein connexin 43 in ureteral ligated kidneys is increased sixfold already 5 days after UUO. In this way, the increased connexin 43 mRNA levels indicate a possible function in the remodeling of the kidney tissue after tubular damage and fibrosis.
肾间质纤维化（RIF）的发展与细胞因子和生长因子的表达及分泌有关。因此，我们在大鼠单侧输尿管梗阻（UUO）模型中，研究了在纤维化的最初迹象可见时，即UUO后第10天之前及当天，以及在进行性RIF过程中，已知为致病因素的细胞因子mRNA表达的时间进程。与对侧肾脏相比，手术15天后，UUO使单核细胞趋化蛋白1的mRNA表达增加了五倍。该水平在第25天之前一直保持约三倍的升高。促纤维化细胞因子转化生长因子β1（TGF-β1）的mRNA在整个时间进程中增加了两到三倍，而血小板衍生生长因子B链（PDGF-B）及其受体β（PDGF-Rβ）的mRNA在UUO后增加，在第10 - 15天达到最大值。PDGF-B mRNA在第15天之前增加，标志着纤维化的开始，此后下降，而PDGF-Rβ mRNA的表达在整个研究期间保持超过三倍的升高。用TGF-β1和/或PDGF-B培养肾成纤维细胞表明，即使它们联合使用，其对细胞生长和增殖的特定作用仍得以维持。TGF-β1和PDGF-B/PDGF-Rβ mRNA水平的持续升高证实了这些细胞因子特别参与RIF发病机制的假设。输尿管结扎肾脏中缝隙连接蛋白连接蛋白43的mRNA表达在UUO后5天就已经增加了六倍。通过这种方式，连接蛋白43 mRNA水平的升高表明其在肾小管损伤和纤维化后肾脏组织重塑中可能发挥作用。
