Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin
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Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin. / Reiser, Jochen; Oh, Jun; Shirato, Isao; Asanuma, Katsuhiko; Hug, Andreas; Mundel, Thomas M; Honey, Karen; Ishidoh, Kazumi; Kominami, Eiki; Kreidberg, Jordan A; Tomino, Yasuhiko; Mundel, Peter.
In: J BIOL CHEM, Vol. 279, No. 33, 13.08.2004, p. 34827-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin
AU - Reiser, Jochen
AU - Oh, Jun
AU - Shirato, Isao
AU - Asanuma, Katsuhiko
AU - Hug, Andreas
AU - Mundel, Thomas M
AU - Honey, Karen
AU - Ishidoh, Kazumi
AU - Kominami, Eiki
AU - Kreidberg, Jordan A
AU - Tomino, Yasuhiko
AU - Mundel, Peter
PY - 2004/8/13
Y1 - 2004/8/13
N2 - Podocyte foot process effacement and disruption of the slit diaphragm are typically associated with glomerular proteinuria and can be induced in rats by the injection of puromycin aminonucleoside. Here, we show that the induction of puromycin aminonucleoside nephrosis involves podocyte migration conducted by a coordinated interplay between the cysteine protease cathepsin L and alpha(3) integrin. Puromycin aminonucleoside treatment up-regulates cathepsin L expression in podocytes in vivo as well as expression and enzymatic activity of cathepsin L in podocytes in vitro. Isolated podocytes from mice lacking cathepsin L are protected from cell puromycin aminonucleoside-induced cell detachment. The functional significance of cathepsin L expression was underscored by the observation that puromycin aminonucleoside-induced cell migration was slowed down in cathepsin L-deficient podocytes and by the preservation of cell-cell contacts and expression of vital slit diaphragm protein CD2AP. Cathepsin L expression and activity were induced in podocytes lacking alpha(3) integrin. Similarly, acute functional inhibition of alpha(3) integrin in wild type podocytes with a blocking antibody increased the expression of cathepsin L activity. Down-regulation of alpha(3) integrin protected against puromycin aminonucleoside-induced podocyte detachment. In summary, these data establish that podocyte foot process effacement is a migratory event involving a novel interplay between cathepsin L and alpha(3) integrin.
AB - Podocyte foot process effacement and disruption of the slit diaphragm are typically associated with glomerular proteinuria and can be induced in rats by the injection of puromycin aminonucleoside. Here, we show that the induction of puromycin aminonucleoside nephrosis involves podocyte migration conducted by a coordinated interplay between the cysteine protease cathepsin L and alpha(3) integrin. Puromycin aminonucleoside treatment up-regulates cathepsin L expression in podocytes in vivo as well as expression and enzymatic activity of cathepsin L in podocytes in vitro. Isolated podocytes from mice lacking cathepsin L are protected from cell puromycin aminonucleoside-induced cell detachment. The functional significance of cathepsin L expression was underscored by the observation that puromycin aminonucleoside-induced cell migration was slowed down in cathepsin L-deficient podocytes and by the preservation of cell-cell contacts and expression of vital slit diaphragm protein CD2AP. Cathepsin L expression and activity were induced in podocytes lacking alpha(3) integrin. Similarly, acute functional inhibition of alpha(3) integrin in wild type podocytes with a blocking antibody increased the expression of cathepsin L activity. Down-regulation of alpha(3) integrin protected against puromycin aminonucleoside-induced podocyte detachment. In summary, these data establish that podocyte foot process effacement is a migratory event involving a novel interplay between cathepsin L and alpha(3) integrin.
KW - Adaptor Proteins, Signal Transducing
KW - Animals
KW - Blotting, Northern
KW - Blotting, Western
KW - Cathepsin L
KW - Cathepsins/metabolism
KW - Cell Differentiation
KW - Cell Line
KW - Cell Movement
KW - Cells, Cultured
KW - Cysteine Endopeptidases
KW - Cytoskeletal Proteins
KW - Down-Regulation
KW - Extracellular Matrix/metabolism
KW - Gene Expression Profiling
KW - Humans
KW - Immunoblotting
KW - Integrin alpha3/metabolism
KW - Integrins/metabolism
KW - Kidney/metabolism
KW - Male
KW - Mice
KW - Microscopy, Fluorescence
KW - Models, Biological
KW - Nephrotic Syndrome/metabolism
KW - Polymerase Chain Reaction
KW - Proteins/metabolism
KW - Puromycin/pharmacology
KW - Rats
KW - Rats, Sprague-Dawley
KW - Up-Regulation
U2 - 10.1074/jbc.M401973200
DO - 10.1074/jbc.M401973200
M3 - SCORING: Journal article
C2 - 15197181
VL - 279
SP - 34827
EP - 34832
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 33
ER -