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Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells
Author(s) -
Morita Yoshikata,
Araki Hisazumi,
Sugimoto Toshiro,
Takeuchi Keisuke,
Yamane Takuya,
Maeda Toshinaga,
Yamamoto Yoshio,
Nishi Katsuji,
Asano Masahide,
Shirahama-Noda Kanae,
Nishimura Mikio,
Uzu Takashi,
Hara-Nishimura Ikuko,
Koya Daisuke,
Kashiwagi Atsunori,
Ohkubo Iwao
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.02.064
Subject(s) - fibronectin , extracellular matrix , endopeptidase , microbiology and biotechnology , endosome , chemistry , extracellular , in vitro , biology , biochemistry , enzyme , intracellular
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.