Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis.
Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis.
复制标题
小鼠狼疮性肾炎肾组织中1型纤溶酶原激活剂抑制剂的表达。
DOI：
10.1038/ki.1995.17
复制
发表时间：
1995
影响因子：
19.6
通讯作者：
Loskutoff,DJ
中科院分区：
文献类型：
--
作者：
Keeton,M;Ahn,C;Eguchi,Y;Burlingame,R;Loskutoff,DJ
1型纤溶酶原激活物抑制物在狼疮性肾炎小鼠肾组织中的表达。许多肾脏疾病与肾小球中的纤维蛋白沉积有关，这种情况反映了凝血和纤维蛋白溶解系统之间的平衡异常。我们最近发现，正常小鼠肾脏含有非常低水平的1型纤溶酶原激活物抑制剂（派-1），一种有效的抗纤溶蛋白，但在内毒素血症，大量的派-1蛋白和mRNA表达在肾小球和管周内皮细胞。这些结果提高了肾小球中派-1过表达可能有助于肾脏疾病中观察到的持续病理学的可能性。为了直接研究这种可能性，我们研究了派-1在MRL/lpr小鼠中的表达，使用原位杂交和免疫组织化学。雌性MRL/lpr小鼠发生早发性狼疮性肾小球肾炎（GN），这是一种在肾小球中检测到纤维蛋白沉积并且抗凝治疗改善预后的疾病。我们检测到非常低水平的派-1 mRNA和抗原在肾血管平滑肌细胞和16只对照小鼠的肾乳头。相比之下，派-1在34只患病小鼠中的33只的整个肾脏中以相对高的水平表达，包括肾小球内以及肾小管和血管中。此外，派-1在组织中的水平似乎与疾病的严重程度相关。派-1表达定位于内皮细胞、壁上皮细胞、肾小管上皮细胞和肾小管上皮细胞浸润的单个核细胞。在正常肾脏中，这些细胞均不表达可检测水平的派-1。派-1在狼疮肾炎小鼠肾脏中的不适当表达表明，这种重要的纤溶抑制剂可能在这种疾病过程的发病机制中发挥作用。
Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis. Many renal diseases are associated with fibrin deposition in the glomeruli, a situation that reflects an abnormality in the balance between the coagulation and fibrinolytic systems. We recently demonstrated that normal mouse kidney contains very low levels of type 1 plasminogen activator inhibitor (PAI-1), a potent anti-fibrinolytic protein, but that during endotoxemia, large amounts of PAI-1 protein and mRNA are expressed in glomerular and peritubular endothelial cells. These results raise the possibility that overexpression of PAI-1 in the glomerulus may contribute to the ongoing pathology seen in renal disease. To directly investigate this possibility, we studied PAI-1 expression in MRL/lprmice, usingin situhybridization and immunohistochemistry. Female MRL/lprmice develop early onset lupus glomerulonephritis (GN), a disease in which fibrin deposition is detected in the glomerulus and in which anti-coagulation therapy improves the prognosis. We detected very low levels of PAI-1 mRNA and antigen in the smooth muscle cells of renal vessels and in the renal papilla of 16 control mice. In contrast, PAI-1 was expressed in relatively high levels throughout the kidneys of 33 out of 34 diseased mice, both within the glomerulus and also in tubules and vessels. Moreover, the level of PAI-1 in the tissues seemed to correlate with the severity of the disease. PAI-1 expression was localized to endothelial cells, parietal epithelial cells, tubular epithelial cells and infiltrating mononuclear cells in the tubulointerstitium. None of these cells express detectable levels of PAI-1 in the normal kidney. The inappropriate expression of PAI-1 in the kidneys of mice with lupus GN suggests that this important inhibitor of fibrinolysis may play a role in the pathogenesis of this disease process.