MACROPHAGES AND PROGRESSIVE RENAL-DISEASE IN EXPERIMENTAL HYDRONEPHROSIS
MACROPHAGES AND PROGRESSIVE RENAL-DISEASE IN EXPERIMENTAL HYDRONEPHROSIS
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DOI：
10.1016/0272-6386(95)90166-3
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发表时间：
1995-07-01
影响因子：
13.2
通讯作者：
DIAMOND, JR
中科院分区：
文献类型：
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作者：
DIAMOND, JR
最近的许多临床和实验研究清楚地表明，进行性肾损伤过程中发生的最初事件之一是肾小球和肾小管间质室的单核细胞浸润。在这份报告中，实验数据支持的作用，浸润性肾巨噬细胞（Mo）作为介导的间质纤维化的过程中阻塞性肾病将审查，因为它属于单侧输尿管梗阻模型大鼠。从该模型的数据中得出的中心病理生物学主题是，纤维化细胞因子，特别是转化生长因子-β，部分是钼衍生的，代表了最初的梗阻后肾脏炎症和肾脏瘢痕形成的晚期发展之间的关键联系。由于输尿管阻塞产生的机械干扰，管状上皮可能产生许多Mo化学引诱物部分。许多物质可以通过这些渗透钼释放;然而，我们的研究集中在转化生长因子β 1上。转化生长因子-β是细胞外基质的重要调节因子，通过其直接作用和调节其他生长因子来维持基质的稳态。我们认为，输尿管结扎后转化生长因子-β 1的表达显著增加，正如许多实验室所检测到的那样，诱导了促纤维化状态，并启动了一系列失调事件，包括金属蛋白酶组织抑制剂的上调。转化生长因子-β 1也可作为一种有效的刺激物，用于将静止的间质成纤维细胞调节为肌成纤维细胞。从治疗的角度来看，靶向这些早期细胞和分子事件可能是非常重要的，在中断间质纤维化反应，长期阻塞性尿路病。(C)1995年由国家肾脏基金会，公司。
Many recent clinical and experimental studies have dearly demonstrated that one of the initial events taking place in the process of progressive renal injury is monocytic infiltration of the glomerular and tubulointerstitial compartments. In this report, experimental data supporting the role of the infiltrating renal macrophage (Mo) as a mediator of interstitial fibrosis during the course of obstructive nephropathy will be reviewed as it pertains to the unilateral ureteral obstruction model in the rat. The central pathobiologic theme drawn on data from this model is that fibrogenic cytokines, especially transforming growth factor-beta, are, in part, Mo-derived and represent pivotal links between the initial postobstructive renal inflammation and the late development of renal scarring. The tubular epithelium, as a consequence of the mechanical disturbance produced by ureteral obstruction, may elaborate a host of Mo chemoattractant moieties. Many substances can be released by these infiltrating Mo; however, our studies have focused on transforming growth factor-beta 1. Transforming growth factor-beta is an important regulator of extracellular matrix, through its direct effects and modulation of other growth factors to maintain matrix homeostasis. We propose that the markedly increased expression of transforming growth facitor-beta 1 following ureteral ligation, as detected by a number of laboratories, induces a profibrogenic state and initiates a cascade of dysregulatory events, including the upregulation of tissue inhibitors of metalloproteinase. Transforming growth factor-beta 1 also may serve as a potent stimulus for the modulation of quiescent interstitial fibroblasts into myofibroblasts. From a therapeutic standpoint, targeting these early cellular and molecular events may be extremely important in interrupting the interstitial fibrotic response to long-term obstructive uropathy. (C) 1995 by the National Kidney Foundation, Inc.