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      Gremlins: Is This What Renal Fibrogenesis Has Come To?

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          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.

          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

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              Gremlins, glomeruli and diabetic nephropathy.

              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.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                27 June 2002
                : 10
                : 4
                : 241-244
                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
                63698 Exp Nephrol 2002;10:241–244
                © 2002 S. Karger AG, Basel

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                Figures: 1, Tables: 1, References: 16, Pages: 4
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