Abstract
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)-beta superfamily. Mesangial cell gremlin mRNA levels were induced by high glucose, cyclic mechanical strain, and TGF-beta1 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 TGFbeta-mediated pathways, and (e) Gremlin is a potential endogenous antagonist of BMPs within a diabetic glomerular milieu.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Amino Acid Sequence
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Animals
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Base Sequence
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / biosynthesis
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Bone Morphogenetic Proteins / chemistry
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Bone Morphogenetic Proteins / genetics
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Glomerular Mesangium / metabolism*
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Glucose / pharmacology*
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Humans
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Intercellular Signaling Peptides and Proteins*
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Kidney Cortex / metabolism*
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Molecular Sequence Data
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Open Reading Frames
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Protein Biosynthesis
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Proteins / chemistry
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Proteins / genetics*
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RNA, Messenger / genetics
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Rats
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Transcription, Genetic
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Transforming Growth Factor beta / pharmacology
Substances
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3' Untranslated Regions
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BMP2 protein, human
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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GREM1 protein, human
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Intercellular Signaling Peptides and Proteins
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Proteins
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RNA, Messenger
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Transforming Growth Factor beta
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Glucose