The interstitial response to renal injury: Fibroblast-like cells show phenotypic changes and have reduced potential for erythropoietin gene expression
The interstitial response to renal injury: Fibroblast-like cells show phenotypic changes and have reduced potential for erythropoietin gene expression
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DOI：
10.1038/ki.1997.387
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发表时间：
1997-09-01
影响因子：
19.6
通讯作者：
Ratcliffe, PJ
中科院分区：
文献类型：
--
作者：
Maxwell, PH;Ferguson, DJP;Ratcliffe, PJ
为了确定受损肾脏中促红细胞生成素基因表达的潜力，在携带同源重组促红细胞生成素-猿猴病毒 40 T 抗原 (Epo-TAg) 转基因的转基因小鼠中检查了标记基因表达。研究了三种类型的肾损伤：输尿管梗阻、肾蒂夹紧后的整体缺血和局灶性针刺损伤。所有损伤模式都与间质空间的扩张有关，其中细胞数量增加。在间质成纤维细胞样细胞中观察到的改变包括细胞过程的数量和复杂性增加、收缩元件（特别是中间丝结蛋白）的表达增强以及胞外5'-核苷酸酶的表达减少。每种类型的损伤后，可被刺激表达 Epo-TAg 的细胞比例都会出现局灶性或普遍性的减少。然而，即使在严重损伤的区域也存在一些阳性染色细胞，并且通过严重贫血或缺氧刺激可以招募更多的细胞来表达Epo-TAg，这表明在这些区域中具有促红细胞生成素基因表达潜力的细胞既不存在也不完全抵抗刺激。在所有受损的肾脏中，Epo-TAg 表达仅限于成纤维细胞样群体。双标记实验表明，表达Epo-TAg的细胞也表达增加量的结蛋白，这表明响应损伤而发展的肌成纤维细胞特征和促红细胞生成素基因表达的能力并不相互排斥。
To define the potential for erythropoietin gene expression in injured kidneys, marker gene expression was examined in transgenic mice bearing a homologously recombined erythropoietin-simian virus 40 T antigen (Epo-TAg) transgene. Three types of renal injury were studied: ureteric obstruction, global ischemia following clamping of the renal pedicle, and focal needlestick injury. All modes of injury were associated with an expansion of the interstitial space, which contained an increased number of cells. Alterations observed in the interstitial fibroblast-like cells included an increased number and complexity of cellular processes, enhanced expression of contractile elements, particularly of the intermediate filament desmin, and reduced expression of ecto-5'-nucleotidase. Following each type of injury there was a focal or general reduction in the proportion of such cells that could be stimulated to express Epo-TAg. However, some positively staining cells were present even in severely injured regions and more could be recruited to express Epo-TAg by severe anemic or hypoxic stimulation, indicating that cells with the potential for erythropoietin gene expression were neither absent nor completely refractory to stimulation in these regions. In all injured kidneys, Epo-TAg expression was limited to the fibroblast-like population. Double labeling experiments showed that cells expressing Epo-TAg also expressed increased amounts of desmin, demonstrating that the myofibroblast features which develop in response to injury and the capacity for erythropoietin gene expression are not mutually exclusive.