Bone Morphogenetic Protein-7 and Connective Tissue Growth Factor: Novel Targets for Treatment of Renal Fibrosis?

Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4 over BMP-7

“…We and others have shown that Grem1 levels increase during DN whereas levels of BMP-7 decrease [33,46]. Strategies that stimulate BMP-7 signalling have been shown to attenuate renal fibrosis [5,[12][13][14][15][16][17], and reductions in Grem1 levels have a similar beneficial effect in mouse models of DN [32,37]. In vivo reduction of Grem1 via siRNA targeting recovered BMP-7 levels, suggesting that elevated Grem1 may have a role in repressing BMP-7 in DN [37].…”

“…Whereas BMP-4 has been shown to contribute to renal fibrosis, conflicting evidence exists for the pro-or anti-fibrotic role of BMP-2 in this process [8][9][10][11]. BMP-7 is thought of as anti-fibrotic, and has been the focus of many groups who demonstrated its anti-fibrotic activity in models of diabetic nephropathy and other kidney fibrotic diseases [5,[12][13][14][15][16][17]. To date, however, efforts to translate these data into BMP-7-centred treatment of fibrosis have been rather slow to develop [18,19] Canonical BMPs signalling involves the Smad pathway, where BMP dimers bind to type I and type II BMP receptors leading to the formation of a hexameric complex, triggering receptor phosphorylation.…”

Effects of Antiproteinuric Intervention on Elevated Connective Tissue Growth Factor (CTGF/CCN-2) Plasma and Urine Levels in Nondiabetic Nephropathy

“…Plasma CTGF levels independently predict end-stage renal disease, intima-media thickness, and mortality in diabetic nephropathy (11,12), supporting a role in intrarenal as well as extrarenal fibrotic processes (13,14). This is underscored by efficacy of CTGF inhibition in experimental models (15). Few data are available, however, on the role of CTGF in nondiabetic chronic kidney disease (CKD), although intra-and extrarenal fibrosis are of well recognized importance in this disease condition (16 -19).…”

Transforming growth factor-β1/Smad3-independent epithelial–mesenchymal transition in type I collagen glomerulopathy

“…56 Recent literature indicates that CTGF and PDGF are potential candidates for investigation. 51,[57][58][59] Incubation of cultured rat mesangial cells with recombinant human CTGF resulted in 64% increase in type I collagen secretion, an increase greater than that seen with incubation in the presence of TGF-β1. Further, CTGF transcripts were increased by twofold in cultured rat mesangial cells that underwent cyclic mechanical strain.…”