Gremlins: Is This What Renal Fibrogenesis Has Come To?

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Abstract

Gremlin is a member of the differential screening-selected gene aberrative in the neuroblastoma (DAN) family of bone morphogenetic protein (BMP) antagonists. Gremlin influences diverse processes in growth, differentiation and development. Increased expression of gremlin has recently been demonstrated in several models of diabetic nephropathy. Gremlin arrests the cell cycle in mesangial cells and has also been shown to be upregulated in transdifferentiated renal proximal tubular cells. This review summarizes emerging evidence implicating gremlin in the pathophysiology of glomerulosclerosis and tubulointerstitial fibrosis. Gremlin is a potential novel therapeutic target in progressive renal diseases.

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Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin.

E Huillard, G Calothy, Carol D. Blair … (2000)

Down-regulated by mos (Drm)/Gremlin is a highly conserved protein whose properties and expression pattern suggest a role in early development, tissue-specific differentiation, and cell transformation. We have investigated the biosynthesis and processing of Drm expressed endogenously in rat fibroblasts or overexpressed following transient or stable transfection. Analysis of metabolically labeled cells revealed that Drm exists in secreted and cell-associated forms that exhibit similar mobilities in SDS-polyacrylamide gel electrophoresis. Protein analysis indicated that Drm is present in two major species: a slow migrating glycosylated form and a nonglycosylated form. Both forms of Drm are able to undergo phosphorylation. Drm is released into the media within 30 min of synthesis and is detectable for up to 4-5 h, whereas the cell-associated form has a half-life of about 1 h. Confocal immunofluorescent microscopy indicates that Drm is present both on the external surface of expressing cells, as well as within the endoplasmic reticulum and the Golgi. Both glycosylated and nonglycosylated forms of Drm exhibit identical distributions and are able to antagonize bone morphogenetic protein signaling. Like the soluble form, the cell-associated forms are capable of binding (125)I-bone morphogenetic protein-4. These properties are consistent with a role for Drm in interfering with signaling and indicate that Drm may act at the cell surface during tissue development and transformation.

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IHG-2, a Mesangial Cell Gene Induced by High Glucose, Is Humangremlin

Catherine Godson, Madeline Murphy, Michael Clarkson … (2000)

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Gremlins, glomeruli and diabetic nephropathy.

C Hensey, Clive McMahon, Christine H Brady … (2000)

There have been major advances in our understanding of the pathogenetic mechanisms of diabetic nephropathy in recent years. Of particular interest is the emerging paradigm of the role that developmentally important genes may play in this process, representing recapitulation of the ontogenic process. This review examines the potential pathophysiological involvement of one such developmental gene gremlin in diabetic nephropathy.

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Author and article information

Journal

Journal ID (publisher-id): EXN

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: 2002

Publication date (Print): 2002

Publication date (Electronic): 27 June 2002

Volume: 10

Issue: 4

Pages: 241-244

Affiliations

Department of Medicine and Therapeutics, Mater Misericordiae Hospital, The Conway Institute for Biomolecular and Biomedical Research, University College Dublin and The Dublin Molecular Medicine Centre, Dublin, Ireland

Article

Publisher ID: 63698 Other ID: Exp Nephrol 2002;10:241–244

DOI: 10.1159/000063698

PubMed ID: 12097827

SO-VID: 942c0a58-8d14-48d0-a5a8-ee42dc3d54ec

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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.

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Gremlins: Is This What Renal Fibrogenesis Has Come To?

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Abstract

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Karger: Nephrology

Most cited references 3

Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin.

IHG-2, a Mesangial Cell Gene Induced by High Glucose, Is Humangremlin

Gremlins, glomeruli and diabetic nephropathy.

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