Lelongt B, Bengatta S, Delauche M, Lund L R, Werb Z, Ronco P M
Institut National de la Santé et de la Recherche Médicale, Unité 489, Hôpital Tenon and Université Pierre et Marie Curie (Paris 6), 75020 Paris, France.
J Exp Med. 2001 Apr 2;193(7):793-802. doi: 10.1084/jem.193.7.793.
Matrix metalloproteinase (MMP)9/gelatinase B is increased in various nephropathies. To investigate its role, we used a genetic approach. Adult MMP9-deficient (MMP9(-/)-) mice showed normal renal histology and function at 3 mo. We investigated the susceptibility of 3-mo-old mice to the accelerated model of anti-glomerular basement membrane nephritis, in which fibrin is an important mediator of glomerular injury and renal impairment. Unexpectedly, nephritis was more severe in MMP9(-/)- than in control mice, as attested by levels of serum creatinine and albuminuria, and the extent of crescents and fibrin deposits. Circulating or deposited immunoglobulin G, interleukin (IL)-1beta, or IL-10 were the same in MMP9(-/-) and MMP9(+/+) mice. However, we found that fibrin is a critical substrate for MMP9, and in its absence fibrin accumulated in the glomeruli. These data indicate that MMP9 is required for a novel protective effect on the development of fibrin-induced glomerular lesions.
基质金属蛋白酶（MMP）9/明胶酶B在多种肾病中表达增加。为研究其作用，我们采用了遗传学方法。成年MMP9基因敲除（MMP9(-/-)）小鼠在3个月时肾脏组织学和功能正常。我们研究了3月龄小鼠对加速型抗肾小球基底膜肾炎模型的易感性，在该模型中，纤维蛋白是肾小球损伤和肾功能损害的重要介质。出乎意料的是，MMP9(-/-)小鼠的肾炎比对照小鼠更严重，血清肌酐水平、蛋白尿、新月体形成程度和纤维蛋白沉积情况均证实了这一点。MMP9(-/-)和MMP9(+/+)小鼠循环或沉积的免疫球蛋白G、白细胞介素（IL）-1β或IL-10水平相同。然而，我们发现纤维蛋白是MMP9的关键底物，在缺乏MMP9时，纤维蛋白在肾小球中积累。这些数据表明，MMP9对纤维蛋白诱导的肾小球病变的发展具有新的保护作用。
