Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells
Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells
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DOI：
10.1016/j.febslet.2007.02.064
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发表时间：
2007-04-03
期刊：
影响因子：
3.5
通讯作者：
Ohkubo, Iwao
中科院分区：
文献类型：
--
作者：
Morita, Yoshikata;Araki, Hisazumi;Ohkubo, Iwao
Legumain/天冬酰胺酰内肽酶（EC 3.4.22.34）是一种新型的半胱氨酸蛋白酶，其在肾近端小管细胞的晚期内体和溶酶体中大量表达。最近，新的证据表明，豆荚蛋白可能在控制细胞外基质周转的各种病理条件，如肿瘤生长/转移和动脉粥样硬化的进展中发挥重要作用。我们初步发现，纯化的豆荚蛋白可以直接降解纤维连接蛋白，细胞外基质的主要成分之一，在体外。因此，我们研究了豆荚蛋白对培养的小鼠肾近端小管细胞中纤维连接蛋白降解的影响。纤连蛋白的加工可以被氯喹（一种溶酶体降解的抑制剂）抑制，并且可以被legumain的过表达增强，这表明纤连蛋白的降解在legumain存在下发生在来自肾近端小管细胞的溶酶体中。此外，在豆类蛋白缺陷小鼠，单侧输尿管梗阻（UUO）诱导的肾间质纤维连接蛋白和肾间质纤维化的蛋白积累显着增强。这些结果表明，豆荚蛋白可能通过降解纤维连接蛋白在肾近端小管细胞的细胞外基质重塑中发挥重要作用。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.