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Vol. 97, No. 2, 2004
Issue release date: June 2004
Section title: Original Paper
Nephron Exp Nephrol 2004;97:e49–e61
(DOI:10.1159/000078406)

Rho-ROCK Signal Pathway Regulates Microtubule-Based Process Formation of Cultured Podocytes – Inhibition of ROCK Promoted Process Elongation

Gao S.-Y. · Li C.-Y. · Chen J. · Pan L. · Saito S. · Terashita T. · Saito K. · Miyawaki K. · Shigemoto K. · Mominoki K. · Matsuda S. · Kobayashi N.
Department of aAnatomy and Embryology, bDepartment of Hygiene, School of Medicine, and cDepartment of Biological Resources, Integrated Center for Science, Ehime University, Ehime, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/27/2003
Accepted: 12/22/2003
Published online: 11/17/2004

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 0

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE

Abstract

Background: Podocytes, renal glomerular visceral epithelial cells, have two kinds of processes, namely major processes containing microtubules (MTs) and foot processes with actin filaments (AFs). The present study investigated how MTs are organized by the Rho-ROCK signal transduction pathway during process formation of podocytes. Method: After induction of differentiation, podocytes of the conditionally immortalized mouse cell line were treated with Y-27632, a specific inhibitor of ROCK, and exoenzyme C3, an inhibitor of RhoA, as well as with forskolin whose effects include inhibition of RhoA, in order to inhibit the Rho-ROCK pathway. Results: Inhibition of ROCK significantly enhanced the formation of thick processes containing MT bundles. Y-27632 promoted process formation even in the presence of latrunculin A which disrupts AFs, strongly suggesting that ROCK directly regulates MT assembly. Treatment with Y-27632 increased MT stability, and stabilized MTs preferentially localized in podocyte processes. Moreover, when treated with a combination of Y-27632 and forskolin, and with Y-27632 and C3 as well, podocytes developed not only MT-based thick processes but also AF-based thin projections. Conclusions: These data indicate a contribution of ROCK in MT organization to promote podocyte process formation, although it was originally thought to regulate AF assembly. AF-based thin projections seem to be induced mainly by inhibition of RhoA and ROCK. The present study reveals a significant role of the Rho-ROCK signal pathway in the reorganization of both MTs and AFs during process formation of podocytes.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/27/2003
Accepted: 12/22/2003
Published online: 11/17/2004

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 0

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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