title: Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan.
authors.forename: Yoshikata
authors.initials: Y
authors.lastname: Morita
authors.forename: Hisazumi
authors.initials: H
authors.lastname: Araki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamane
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Maeda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Katsuji
authors.initials: K
authors.lastname: Nishi
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Kanae
authors.initials: K
authors.lastname: Shirahama-Noda
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hara-Nishimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohkubo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005109:Extracellular Matrix / Q000201:enzymology* / Q000473:pathology; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D005355:Fibrosis; D007674:Kidney Diseases / Q000201:enzymology* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D000099240:Asparaginyl Endopeptidase
chemical_list: D003546:Cysteine Endopeptidases; D005353:Fibronectins; D000099240:Asparaginyl Endopeptidase