Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome
Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome
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DOI：
10.1016/s0002-9440(10)64541-5
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发表时间：
2000-07-01
影响因子：
6
通讯作者：
Miner, JH
中科院分区：
文献类型：
--
作者：
Andrews, KL;Betsuyaku, T;Miner, JH
基质金属蛋白酶具有基质降解作用：与许多生物过程有关的酶，包括发育和炎症。明胶酶 B（gelB；也称为 MMP-9）在肾脏中表达，推测其参与基底膜重塑和防止肾脏中细胞外基质的致病性积聚。在后肾器官培养物中抑制 gelB 活性会破坏输尿管芽的分支形态发生，表明 gelB 在体内肾脏发育中发挥作用。我们研究了 gelB 缺陷小鼠的肾脏，以寻找发育、组织学、分子、超微结构和功能缺陷。令人惊讶的是，在 gelB-/- 和对照肾脏之间没有检测到差异，并且 gelB 突变体的肾功能正常。此外，gelB-/-胚胎肾脏发育正常。在器官培养中，将明胶酶B缺陷型小鼠与Alport综合征模型Col4a3-/-小鼠交配，以确定gelB是否影响肾小球肾炎的进展。这是一个重要的问题，因为人们假设蛋白酶参与损伤 Alport 肾小球基底膜。然而，gelB的存在与否并不影响肾脏疾病的进展速度。因此，gelB 在正常肾脏中没有明显的作用，并且 gelB 不参与 Alport 综合征小鼠模型中肾小球肾炎的进展。
Matrix metalloproteinases are matrix degrading: enzymes implicated in many biological processes, including development and inflammation. Gelatinase B (gelB; also known as MMP-9) is expressed in the kidney and is hypothesized to be involved in basement membrane remodeling and in preventing pathogenic accumulation of extracellular matrix in the kidney. Inhibition of gelB activity in metanephric organ culture disrupts branching morphogenesis of the ureteric bud, suggesting that gelB plays a role in kidney development in vivo. We studied kidneys of gelB-deficient mice to search for developmental, histological, molecular, ultrastructural, and functional defects. Surprisingly, no differences between gelB-/- and control kidneys were detected, and renal function was normal in gelB mutants. in addition, gelB-/- embryonic kidneys developed normally In organ culture, Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether gelB influences the progression of glomerulonephritis. This is an important question, as it has been hypothesized that proteases are involved in damaging Alport glomerular basement membrane. However, the presence or absence of gelB did not affect the rate of progression of renal disease. Thus, gelB does not have a discernible role in the normal kidney and gelB is not involved in the progression of glomerulonephritis In a mouse model of Alport syndrome.