How Does G-CSF Act on the Kidney during Acute Tubular Injury?

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

Recent findings in stem cell research have demonstrated multi-lineage plasticity of bone marrow cells, and also the contribution of hematopoietic bone marrow stem cells to the regeneration of injured organs including the kidney. These findings suggested the possibility of the use of granulocyte colony-stimulating factor (G-CSF) as a therapeutic option to regenerate injured organs. Recently, several studies regarding the effect of G-CSF on renal function have been reported in mouse models of acute renal failure. This series of experiments provided potentially important information regarding the treatment of patients with renal injury. This review summarizes the possible actions of G-CSF on the kidney, especially during acute tubular injury caused by toxic or ischemic insults.

Related collections

Most cited references 13

Record: found
Abstract: found
Article: not found

Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells.

David Scadden, Jeremy Duffield, R. Kelley … (2005)

Ischemia causes kidney tubular cell damage and abnormal renal function. The kidney is capable of morphological restoration of tubules and recovery of function. Recently, it has been suggested that cells repopulating the ischemically injured tubule derive from bone marrow stem cells. We studied kidney repair in chimeric mice expressing GFP or bacterial beta-gal or harboring the male Y chromosome exclusively in bone marrow-derived cells. In GFP chimeras, some interstitial cells but not tubular cells expressed GFP after ischemic injury. More than 99% of those GFP interstitial cells were leukocytes. In female mice with male bone marrow, occasional tubular cells (0.06%) appeared to be positive for the Y chromosome, but deconvolution microscopy revealed these to be artifactual. In beta-gal chimeras, some tubular cells also appeared to express beta-gal as assessed by X-gal staining, but following suppression of endogenous (mammalian) beta-gal, no tubular cells could be found that stained with X-gal after ischemic injury. Whereas there was an absence of bone marrow-derived tubular cells, many tubular cells expressed proliferating cell nuclear antigen, which is reflective of a high proliferative rate of endogenous surviving tubular cells. Upon i.v. injection of bone marrow mesenchymal stromal cells, postischemic functional renal impairment was reduced, but there was no evidence of differentiation of these cells into tubular cells of the kidney. Thus, our data indicate that bone marrow-derived cells do not make a significant contribution to the restoration of epithelial integrity after an ischemic insult. It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia.

0 comments Cited 136 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury.

Brandon J. Isaac, Shelly K Weiss, Florian Tögel … (2005)

Stem cell and leukocyte migration during homeostasis and inflammation is regulated by a number of chemokines. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are important mediators of leukocyte homeostasis. The postischemic kidney has been shown to recruit different leukocyte populations, including bone marrow-derived stem cells. Therefore, we investigated the SDF-1/CXCR4 system in the kidney after ischemic acute renal failure (ARF). We used immunohistochemistry, in situ hybridization, enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect SDF-1 and CXCR4 in the normal kidney and the kidney after ischemia/reperfusion (I/R) ARF. Mobilization was assessed by flow cytometry for CD34 and colony assays. We show that SDF-1 is expressed in the normal mouse kidney and tubular cells express CXCR4. SDF-1 expression in the kidney increases after I/R induced ARF and decreases in the bone marrow, thereby reversing the normal gradient between bone marrow and the periphery. This causes mobilization of CD34-positive cells into the circulation and their subsequent homing to the kidney with ARF. In vitro and in vivo chemotaxis of bone marrow cells toward damaged kidney epithelium is reversibly inhibited by anti-CXCR4 antibodies. Our data show that renal SDF-1 is a currently unrecognized mediator of homing to and migration of CXCR4 expressing cells in the injured kidney. Because certain cells that express CXCR4 may have renoprotective effects, our results suggest that SDF-1 may be a major signal involved in kidney repair.

0 comments Cited 88 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes.

Katsuhisa Matsuura, Weidong Zhu, Issei Komuro … (2005)

Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial regeneration by promoting mobilization of bone marrow stem cells to the injured heart after myocardial infarction, but the precise mechanisms of the beneficial effects of G-CSF are not fully understood. Here we show that G-CSF acts directly on cardiomyocytes and promotes their survival after myocardial infarction. G-CSF receptor was expressed on cardiomyocytes and G-CSF activated the Jak/Stat pathway in cardiomyocytes. The G-CSF treatment did not affect initial infarct size at 3 d but improved cardiac function as early as 1 week after myocardial infarction. Moreover, the beneficial effects of G-CSF on cardiac function were reduced by delayed start of the treatment. G-CSF induced antiapoptotic proteins and inhibited apoptotic death of cardiomyocytes in the infarcted hearts. G-CSF also reduced apoptosis of endothelial cells and increased vascularization in the infarcted hearts, further protecting against ischemic injury. All these effects of G-CSF on infarcted hearts were abolished by overexpression of a dominant-negative mutant Stat3 protein in cardiomyocytes. These results suggest that G-CSF promotes survival of cardiac myocytes and prevents left ventricular remodeling after myocardial infarction through the functional communication between cardiomyocytes and noncardiomyocytes.

0 comments Cited 87 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: 2006

Publication date (Print): November 2006

Publication date (Electronic): 11 August 2006

Volume: 104

Issue: 4

Pages: e123-e128

Affiliations

Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan

Article

Publisher ID: 94962 Other ID: Nephron Exp Nephrol 2006;104:e123–e128

DOI: 10.1159/000094962

PubMed ID: 16902315

SO-VID: 2c1c297d-b35f-4513-ae61-cb4aef025947

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 : 24 March 2006

Date accepted : 17 May 2006

Page count

Figures: 1, Tables: 1, References: 20, Pages: 1

Comments

Comment on this article

scite_

Cited by 5

See all cited by

Most referenced authors 225

See all reference authors

- Version 1

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

Submit here before July 31, 2024

How Does G-CSF Act on the Kidney during Acute Tubular Injury?

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 13

Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells.

Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury.

G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 222

Cited by 5

Most referenced authors 225