Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin.

Abstract	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.
Authors	Jochen Reiser, Jun Oh, Isao Shirato, Katsuhiko Asanuma, Andreas Hug, Thomas M Mundel, Karen Honey, Kazumi Ishidoh, Eiki Kominami, Jordan A Kreidberg, Yasuhiko Tomino, Peter Mundel
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 33 Pg. 34827-32 (Aug 13 2004) ISSN: 0021-9258 [Print] United States
PMID	15197181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Adaptor Proteins, Signal Transducing CD2-associated protein Cytoskeletal Proteins Integrin alpha3 Integrins Proteins Puromycin Cathepsins Cysteine Endopeptidases CTSL protein, human Cathepsin L Ctsl protein, mouse Ctsl protein, rat
Topics	Adaptor Proteins, Signal Transducing Animals Blotting, Northern Blotting, Western Cathepsin L Cathepsins (metabolism) Cell Differentiation Cell Line Cell Movement Cells, Cultured Cysteine Endopeptidases Cytoskeletal Proteins Down-Regulation Extracellular Matrix (metabolism) Gene Expression Profiling Humans Immunoblotting Integrin alpha3 (metabolism) Integrins (metabolism) Kidney (metabolism) Male Mice Microscopy, Fluorescence Models, Biological Nephrotic Syndrome (metabolism, pathology) Polymerase Chain Reaction Proteins (metabolism) Puromycin (pharmacology) Rats Rats, Sprague-Dawley Up-Regulation

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!