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J Biol Chem, Vol. 275, Issue 14, 9901-9904, April 7, 2000

ACCELERATED PUBLICATION
IHG-2, a Mesangial Cell Gene Induced by High Glucose, Is Human gremlin
REGULATION BY EXTRACELLULAR GLUCOSE CONCENTRATION, CYCLIC MECHANICAL STRAIN, AND TRANSFORMING GROWTH FACTOR-1^*

Ruth McMahon^**, Madeline Murphy^**, Michael Clarkson^**, Maarten Taal^§, Harald S. Mackenzie^§, Catherine Godson^**, Finian Martin^¶, and Hugh R. Brady^**

From the  Conway Institute of Biomolecular and Biomedical Research, ^** Centre for Molecular Inflammation and Vascular Research, Department of Medicine and Therapeutics, University College Dublin, Mater Misericordiae Hospital, Dublin 7, Ireland, the ^§ Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, and the ^¶ Department of Pharmacology, University College Dublin, Belfield, Dublin 4, Ireland

We used cloning in silico coupled with polymerase chain reaction to demonstrate that IHG-2 is part of the 3'-untranslated region of gremlin, a member of the DAN family of secreted proteins that antagonize the bioactivities of members of the transforming growth factor (TGF)- superfamily. Mesangial cell gremlin mRNA levels were induced by high glucose, cyclic mechanical strain, and TGF-1 in vitro, and gremlin mRNA levels were elevated in the renal cortex of rats with streptozotocin-induced diabetic nephropathy in vivo. gremlin expression was observed in parallel with induction of bone morphogenetic protein-2 (BMP-2), a target for gremlin in models of cell differentiation. Together these data indicate that (a) IHG-2 is gremlin, (b) gremlin is expressed in diabetic nephropathy in vivo, (c) both glycemic and mechanical strain stimulate mesangial cell gremlin expression in vitro, (d) high glucose induces gremlin, in part, through TGF-mediated pathways, and (e) Gremlin is a potential endogenous antagonist of BMPs within a diabetic glomerular milieu.

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^* This work was supported by a grant from the Health Research Board, Ireland.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Medicine and Therapeutics, Mater Misericordiae Hospital, University College Dublin, 41 Eccles St., Dublin 7, Ireland. Tel.: 353-1-803 7419; Fax: 353-1-830 8404; E-mail: hrbrady@mater.ie.

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Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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