Expression of subunits of the metalloendopeptidase meprin in renal cortex in experimental hydronephrosis.
Expression of subunits of the metalloendopeptidase meprin in renal cortex in experimental hydronephrosis.
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实验性肾积水肾皮质金属内肽酶 meprin 亚基的表达。
DOI：
10.1152/ajprenal.1996.270.4.f669
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Diamond,JR
中科院分区：
文献类型：
--
作者：
Ricardo,SD;Bond,JS;Johnson,GD;Kaspar,J;Diamond,JR
Meprin A是啮齿动物近端肾小管上皮中的金属内肽酶，其能够水解多种肽和蛋白质。本研究的目的是探讨输尿管结扎对meprin亚基表达的影响。输尿管结扎导致在12小时内输尿管梗阻的α和β-meprin亚基的表达显着下降。在输尿管结扎后24、48和96 h，发现meprin α和β mRNA表达下调幅度更大。在单侧输尿管梗阻后24小时（UUO后），梗阻肾中meprin α亚基（与对照组相比减少20倍）和48小时meprin β亚基（减少90倍）中meprin mRNA表达的最大减少发生在对侧未梗阻对照肾（CUK）。在免疫标记，强度为两个meprin亚基在皮质髓质交界处显着下降，在24至96小时后，输尿管结扎的CUK标本相比。原位杂交结果表明，CUK标本表达meprin β-mRNA的皮质髓质交界处，而阻塞的肾脏表现出meprin β-亚基的mRNA信号减少。在UUO后96小时的评估中，UUO大鼠肾脏中的间质巨噬细胞数量稳步增加。艾德-1阳性巨噬细胞几乎仅在肾小管周围皮质间质中观察到，呈环状模式，肾小球周围巨噬细胞簇占优势。出乎意料的是，逆转UUO后，间质巨噬细胞数量仍然高于对照组，尽管肾盂和肾盏系统明显减压。总之，本研究证实了在UUO数小时内meprin α和β的下调，并表明了输尿管梗阻的一种新的肾小管反应。
Meprin A is a metalloendopeptidase in the proximal tubular epithelium of rodents that is capable of hydrolyzing a great variety of peptides and proteins. The aim of the present investigation was to investigate effects of ureteral ligation on the expression of meprin subunits. Ureteral ligation resulted in marked decreases in the expression of both alpha- and beta-meprin subunits within 12 h of ureteral obstruction. Even greater downregulation of expression of meprin alpha- and beta-mRNA was noted at 24, 48, and 96 h after ureteral ligation. The greatest decrease in meprin mRNA expression in obstructed kidneys over contralateral unobstructed control kidneys (CUK) occurred at 24 h postunilateral ureteral obstruction (post-UUO) for the meprin alpha-subunit (20-fold decrease compared with controls) and at 48 h for the meprin beta-subunit (90-fold decrease). On immunolabeling, the intensity for the two meprin subunits at the corticomedullary junction was dramatically decreased at 24 to 96 h after ureteral ligation in contrast to the CUK specimens. Results of in situ hybridization indicated that the CUK specimens expressed meprin beta-mRNA at the corticomedullary junction, whereas the obstructed kidneys exhibited a decrease in mRNA signal for meprin beta-subunit. There was a steady increase in the interstitial macrophage number in UUO rat kidneys over the 96 h of evaluation post-UUO. ED-1-positive macrophages were observed almost exclusively in the peritubular cortical interstitial space in a ringlike pattern with a preponderance of macrophage clusters around glomeruli. Unexpectedly, after reversal of UUO, the interstitial macrophage number remained higher than controls, despite the demonstrable decompression of the renal pelvis and caliceal system. In summary, this investigation demonstrates downregulation of meprin alpha and beta within hours of UUO and indicates a novel tubular response to ureteral obstruction.