The role of meprin A in the pathogenesis of acute renal failure.
The role of meprin A in the pathogenesis of acute renal failure.
复制标题
meprin A 在急性肾衰竭发病机制中的作用。
DOI：
10.1006/bbrc.1995.1366
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Bond,JS
中科院分区：
文献类型：
--
作者：
Trachtman,H;Valderrama,E;Dietrich,JM;Bond,JS
Meprin A是一种锌依赖的金属内肽酶，存在于肾近端小管上皮细胞刷状缘膜上。虽然该酶已在哺乳动物的肾脏中被检测到，其生化结构和作用也已被确定，但该内肽酶在正常肾脏生理和疾病状态中的作用尚不清楚。因此，我们评估了近交系正常和低meprin A活性的小鼠对缺血性和肾毒性急性肾功能衰竭的易感性。我们报告了两个正常的meprin A品系，C57BL/6和DBA/2，与两个低meprin A品系C3H/He和CBA相比，在双侧肾动脉夹闭或注射高渗甘油后，发生了更严重的肾脏功能和结构损伤。这些发现表明，梅普林A在各种肾脏损害后急性肾功能衰竭的病理生理学中起作用。我们认为，在急性肾功能衰竭期间，这种金属内肽酶重新分布到基底外侧膜域，导致细胞外基质的降解和邻近小管周围结构的损害。
Meprin A is a zinc-dependent metallo-endopeptidase that is present in the brush border membrane of renal proximal tubular epithelial cells. Although this enzyme has been detected in the kidney of mammalian species and its biochemical structure and action have been characterized, the role of this endopeptidase in normal renal physiology and in disease states is unknown. Therefore, we assessed the susceptibility of inbred strains of mice with normal and low meprin A activity to ischemic and nephrotoxic acute renal failure. We report that two normal meprin A strains of mice, C57BL/6 and DBA/2, developed more severe renal functional and structural injury following either bilateral renal artery clamping or the injection of hypertonic glycerol, compared to two low meprin A strains, C3H/He and CBA. These findings suggest that meprin A plays a role in the pathophysiology of acute renal failure following a variety of insults to the kidney. We propose that redistribution of this metalloendopeptidase to the basolateral membrane domain during acute renal failure results in degradation of the extracellular matrix and damage to adjacent peritubular structures.