help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morigi, M.
Right arrow Articles by Benigni, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morigi, M.
Right arrow Articles by Benigni, A.
(American Journal of Pathology. 2005;166:1309-1320.)
© 2005 American Society for Investigative Pathology

In Response to Protein Load Podocytes Reorganize Cytoskeleton and Modulate Endothelin-1 Gene

Implication for Permselective Dysfunction of Chronic Nephropathies

Marina Morigi*, Simona Buelli*, Stefania Angioletti*, Cristina Zanchi*, Lorena Longaretti*, Carla Zoja*, Miriam Galbusera*, Sara Gastoldi*, Peter Mundel{dagger}, Giuseppe Remuzzi*{ddagger} and Ariela Benigni*

From the ‘Mario Negri’ Institute for Pharmacological Research,* Bergamo, Italy; the Division of Nephrology and Dialysis,{ddagger} Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy; and the Department of Medicine,{dagger} Albert Einstein College of Medicine, New York, New York

Effacement of podocyte foot processes occurs in many proteinuric nephropathies and is accompanied by rearrangement of the actin cytoskeleton. Here, we studied whether protein overload affects intracellular pathways, leading to cytoskeletal architecture changes and ultimately to podocyte dysfunction. Mouse podocytes bound and endocytosed both albumin and IgG via receptor-specific mechanisms. Protein overload caused redistribution of F-actin fibers instrumental to up-regulation of the prepro-endothelin (ET)-1 gene and production of the corresponding peptide. Increased DNA-binding activity for nuclear factor (NF)-{kappa}B and Ap-1 nuclear proteins was measured in nuclear extracts of podocytes exposed to excess proteins. Both Y27632, which inhibits Rho kinase-dependent stress fiber formation, and jasplakinolide, an F-actin stabilizer, decreased NF-{kappa}B and Ap-1 activity and reduced ET-1 expression. This suggested a role for the cytoskeleton, through activated Rho, in the regulation of the ET-1 peptide. Focal adhesion kinase (FAK), an integrin-associated nonreceptor tyrosine kinase, was phosphorylated by albumin treatment via Rho kinase-triggered actin reorganization. FAK activation led to NF-{kappa}B- and Ap-1-dependent ET-1 expression. These data suggest that reorganization of the actin cytoskeletal network in response to protein load is implicated in modulation of the ET-1 gene via Rho kinase-dependent FAK activation of NF-{kappa}B and Ap-1 in differentiated podocytes. Increased ET-1 generation might alter glomerular permselectivity and amplify the noxious effect of protein overload on dysfunctional podocytes.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
F. Collino, B. Bussolati, E. Gerbaudo, L. Marozio, S. Pelissetto, C. Benedetto, and G. Camussi
Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells
Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1185 - F1194.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. Hidaka, Y. Suzuki, M. Yamashita, T. Shibata, Y. Tanaka, S. Horikoshi, and Y. Tomino
Amelioration of Crescentic Glomerulonephritis by RhoA Kinase Inhibitor, Fasudil, through Podocyte Protection and Prevention of Leukocyte Migration
Am. J. Pathol., March 1, 2008; 172(3): 603 - 614.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Castelletti, R. Donadelli, F. Banterla, F. Hildebrandt, P. F. Zipfel, E. Bresin, E. Otto, C. Skerka, A. Renieri, M. Todeschini, et al.
Mutations in FN1 cause glomerulopathy with fibronectin deposits
PNAS, February 19, 2008; 105(7): 2538 - 2543.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Akilesh, T. B. Huber, H. Wu, G. Wang, B. Hartleben, J. B. Kopp, J. H. Miner, D. C. Roopenian, E. R. Unanue, and A. S. Shaw
From the Cover: Podocytes use FcRn to clear IgG from the glomerular basement membrane
PNAS, January 22, 2008; 105(3): 967 - 972.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
X. Yang, H.-C. Huang, H. Yin, R. J. Alpern, and P. A. Preisig
RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3
Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1054 - F1064.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. Zhang, A. V. Cybulsky, L. Aoudjit, J. Zhu, H. Li, N. Lamarche-Vane, and T. Takano
Role of Rho-GTPases in complement-mediated glomerular epithelial cell injury
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F148 - F156.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. Shalamanova, F. McArdle, A. B. Amara, M. J. Jackson, and R. Rustom
Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor
Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1846 - F1857.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. R. Reddy, M. J. Pushpanathan, R. F. Ransom, L. B. Holzman, F. C. Brosius III, M. Diakonova, P. Mathieson, M. A. Saleem, E. O. List, J. J. Kopchick, et al.
Identification of the Glomerular Podocyte as a Target for Growth Hormone Action
Endocrinology, May 1, 2007; 148(5): 2045 - 2055.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Eyre, K. Ioannou, B. D. Grubb, M. A. Saleem, P. W. Mathieson, N. J. Brunskill, E. I. Christensen, and P. S. Topham
Statin-sensitive endocytosis of albumin by glomerular podocytes
Am J Physiol Renal Physiol, February 1, 2007; 292(2): F674 - F681.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Morigi, S. Buelli, C. Zanchi, L. Longaretti, D. Macconi, A. Benigni, D. Moioli, G. Remuzzi, and C. Zoja
Shigatoxin-Induced Endothelin-1 Expression in Cultured Podocytes Autocrinally Mediates Actin Remodeling
Am. J. Pathol., December 1, 2006; 169(6): 1965 - 1975.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. Barton, J. J. Mullins, M. A. Bailey, and M. Kretzler
Role of Endothelin Receptors for Renal Protection and Survival in Hypertension: Waiting for Clinical Trials
Hypertension, November 1, 2006; 48(5): 834 - 837.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
N. Dhaun, J. Goddard, and DavidJ. Webb
The Endothelin System and Its Antagonism in Chronic Kidney Disease
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Pfab, C. Thone-Reineke, F. Theilig, I. Lange, H. Witt, C. Maser-Gluth, M. Bader, J.-P. Stasch, P. Ruiz, S. Bachmann, et al.
Diabetic Endothelin B Receptor-Deficient Rats Develop Severe Hypertension and Progressive Renal Failure
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1082 - 1089.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.