Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells
- 作者：Yoshikata Morita ; Hisazumi Araki ; Toshiro Sugimoto ; Keisuke Takeuchi ; Takuya Yamane ; Toshinaga Maeda ; Yoshio Yamamoto ; Katsuji Nishi ; Masahide Asano ; Kanae Shirahama-Noda ; et al.
- 关键词：Extracellular matrix remodeling ; Fibronectin ; Legumain ; Lysosomal peptidase ; Renal proximal tubular cell ; Unilateral ureteral obstruction
- 刊名：FEBS Letters
- 出版年：2007
- 期刊代码：70_00145793
- 类别：bio
- 出版时间：3 April 2007
- 卷：581
- 期：7
- 页码：1417-1424
- 文件大小：716 K
摘要
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.