Lee Rutha, Eidman Keith E, Kren Stefan M, Hostetter Thomas H, Segal Yoav
Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minn., USA.
Nephron Exp Nephrol. 2004;97(2):e62-70. doi: 10.1159/000078407.
BACKGROUND/AIM: The discoidin domain receptors (DDRs) DDR1 and DDR2 are cardinal members of a receptor tyrosine kinase subfamily, activated by collagens. They are candidate effectors in tissue injury and fibrosis. We investigated the DDR expression in normal and remnant rat kidneys.
The DDR expression in kidney and other tissues was examined by indirect immunofluorescence, immunoblotting, and ribonuclease protection assays. The expression patterns in remnant and control kidneys were compared at 2-, 4-, and 8-week time points, following induction of injury.
DDR1 is expressed in basolateral membranes of select nephron segments, from the connecting tubule to the renal papilla. DDR2 is expressed in apical membranes of select nephron segments, from the loop of Henle to the macula densa. The DDR1 protein expression is upregulated within the glomeruli of remnant kidneys. The distribution of DDR2 in remnant kidneys is similar to that in controls. The DDR mRNA levels in remnant and control kidneys were not significantly different, at any time point.
The DDR1 localization in the rat kidney is consistent with roles in cell-matrix interactions. Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions.
背景/目的:盘状结构域受体(DDR)DDR1和DDR2是受体酪氨酸激酶亚家族的主要成员,由胶原蛋白激活。它们是组织损伤和纤维化的潜在效应分子。我们研究了DDR在正常和残余大鼠肾脏中的表达情况。
通过间接免疫荧光、免疫印迹和核糖核酸酶保护试验检测肾脏及其他组织中DDR的表达。在诱导损伤后的2周、4周和8周时间点,比较残余肾脏和对照肾脏中的表达模式。
DDR1表达于从连接小管到肾乳头的特定肾单位节段的基底外侧膜。DDR2表达于从髓袢到致密斑的特定肾单位节段的顶端膜。DDR1蛋白表达在残余肾脏的肾小球内上调。DDR2在残余肾脏中的分布与对照相似。在任何时间点,残余肾脏和对照肾脏中的DDR mRNA水平均无显著差异。
DDR1在大鼠肾脏中的定位与其在细胞-基质相互作用中的作用一致。残余肾脏肾小球内的上调提示其在肾脏损伤中可能具有其他作用。DDR2在成年大鼠肾脏中的定位与其在细胞-基质相互作用中的作用不一致。