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-beta 1

We used cloning in silico coupled with polymerase chain reaction to demonst rate 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, Mesangia l cell gremlin mRNA levels were induced by high glucose, cyclic mechanical strain, and TGF-beta 1 in vitro, and gremlin mRNA levels were elevated in t he renal cortex of rats with streptozotocin-induced diabetic nephropathy in vivo. gremlin expression was observed in parallel with induction of bone m orphogenetic protein-2 (BMP-2), a target for gremlin in models of cell diff erentiation. Together these data indicate that (a) IHG-2 is gremlin, (b) gr emlin is expressed in diabetic nephropathy in vivo, (c) both glycemic and m echanical strain stimulate mesangial cell gremlin expression in vitro, (d) high glucose induces gremlin, in part, through TGF beta-mediated pathways, and (e) Gremlin is a potential endogenous antagonist of BMPs within a diabe tic glomerular milieu.