Extracellular Actin Impairs Glomerular Capillary Repair in Experimental Mesangioproliferative Glomerulonephritis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Exogenous administration of actin prevents tumour growth in mice by specifically antagonizing angiogenin, a potent inducer of neovascularization. To investigate whether the angiogenin/actin system is also of importance in renal disease, we examined the effect of actin during glomerular capillary repair in anti-Thy-1.1 mesangioproliferative glomerulonephritis. Male Wistar rats were injected intravenously with actin, a control protein, i.e. albumin, or vehicle alone at 8, 16, 24, 32, 40 and 48 h after disease induction. On day 8, actin-treated rats showed significantly more microaneurysms and persistent mesangiolysis as compared to both control groups. This was associated with increased proteinuria in actin-treated rats. Moreover, actin-treated rats showed increased counts of glomerular macrophages (+40%) and polymorphonuclear leukocytes (+100%) on day 3 as well as a decrease in glomerular endothelial area on days 3 and 8. However, no difference in early glomerular endothelial as well as non-endothelial cell proliferation was noted in actin-treated rats as compared to controls. Actin treatment had no apparent influence on mesangial cell activation (i.e. de novo expression of α-smooth muscle actin) or glomerular accumulation of fibronectin or type IV collagen. Additional in vitro studies demonstrated that extracellular actin inhibits the angiogenin but not VEGF<sub>165</sub>-induced proliferation of (glomerular) endothelial cells. Moreover, actin inhibited other, yet unidentified, serum-derived angiogenic factors. In conclusion, exogenous actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis possibly due to interference with angiogenic factors such as angiogenin. Our combined in vivo and in vitro observations suggest that the release of intracellular actin during mesangiolysis is an endogenous pathway by which glomerular capillary damage is augmented.

Related collections

Most cited references 7

Record: found
Abstract: found
Article: found

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Akira Shimizu, Yukinari Masuda, Hiroshi Kitamura … (1998)

Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Susbsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4–6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 ± 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 ± 0.00 in controls, mean ± SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10–30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.

0 comments Cited 10 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Angiogenin enhances actin acceleration of plasminogen activation.

Alan J. Riordan, G Hu (1993)

Angiogenin interacts with actin to form a complex, which like actin itself, can accelerate plasmin generation by tissue plasminogen activator (tPA). In contrast to actin, the angiogenin-actin complex does not inhibit plasmin activity. In the presence of the angiogenin-actin complex, the overall proteolytic activity of a mixture of plasminogen and tPA is 11-fold higher than in its absence and 6-fold higher than in the presence of actin alone. These results suggest that binding and displacement of cell surface actin by angiogenin might be involved in cell migration and tumor invasion, processes that depend on the proteolytic degradation of basement membrane and the extracellular matrix. Therefore, the activity of the angiogenin-actin complex reported here may have physiological and pathological significance in the process of angiogenin-induced angiogenesis.

0 comments Cited 8 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of angiogenin expression in human HepG2 hepatoma cells by mediators of the acute-phase response.

S J Verselis, K A Olson, J W Fett (1999)

Angiogenin is a potent inducer of neovascularization in vivo. However, like other angiogenic molecules, its specific physiologic roles and mechanisms regulating its expression remain to be elucidated. Angiogenin is a liver-derived component of normal serum whose concentration can increase in various disease states. This suggests that it might participate in the acute-phase response. In an initial study we showed that angiogenin protein and mRNA levels transiently increased in mice following an acute inflammatory stimulus. We now report that IL-6, a major inducer of acute-phase proteins, stimulates the synthesis and secretion of angiogenin protein in human HepG2 cells within 24 hr following treatment, an effect enhanced by dexamethasone. IL-6 also increases the amount of angiogenin mRNA without altering its half-life. This increase, suppressible by cycloheximide, peaks at 12 hr following stimulation and returns to basal levels by 48 hr. IL-1 alone slightly decreases the basal production of angiogenin protein and mRNA, but essentially abolishes the response to IL-6 in the absence or presence of dexamethasone. This antagonistic effect by IL-1 on IL-6 activity is not a result of changes in mRNA stability nor is it dependent on new protein synthesis. Thus, the combined effects of IL-6, IL-1, glucocorticoids, and perhaps other related factors may specifically control angiogenin expression. Since angiogenin is regulated in a manner similar to that of acute phase proteins both in vitro and in vivo, it may play a role in the host response to injury.

0 comments Cited 7 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): NEE

Journal ID (nlm-ta): Nephron Exp Nephrol

Journal ID (doi): 10.1159/issn.1660-2129

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISSN (Electronic): 1660-2129

Publication date Subscription-year: 2003

Publication date (Print): April 2003

Publication date (Electronic): 17 November 2004

Volume: 93

Issue: 4

Pages: e158-e167

Affiliations

Divisions of Nephrology, Universities of ^aAachen and ^bHamburg, Germany; ^cDepartment of Pathology, University of Geneva, Switzerland; ^dDepartment of Clinical Pathology, UniversityofVienna,Austria

Article

Publisher ID: 70240 Other ID: Nephron Exp Nephrol 2003;93:e158–e167

DOI: 10.1159/000070240

PubMed ID: 12759577

SO-VID: 8a0eb5ae-3d02-49e1-a819-dab14c84af25

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. 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 government 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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 23 January 2002

Date accepted : 04 December 2002

Page count

Figures: 5, Tables: 1, References: 37, Pages: 1

Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

Submit here before July 31, 2024

Extracellular Actin Impairs Glomerular Capillary Repair in Experimental Mesangioproliferative Glomerulonephritis

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 7

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Angiogenin enhances actin acceleration of plasminogen activation.

Regulation of angiogenin expression in human HepG2 hepatoma cells by mediators of the acute-phase response.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 95

Most referenced authors 41