BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis

The American Journal of Physiology
Tino D PiscioneNorman D Rosenblum

Abstract

The bone morphogenetic proteins, BMP-2 and OP-1, are candidates for growth factors that control renal branching morphogenesis. We examined their effects in embryonic kidney explants and in the mIMCD-3 cell model of collecting duct morphogenesis (mIMCD-3 cells are derived from the terminal inner medullary collecting duct of the SV40 mouse). Osteogenic protein-1 (OP-1), at a dose of 0.25 nM, increased explant growth by 30% (P = 0.001). In contrast, 100-fold greater concentrations of OP-1 (28 nM) decreased explant growth by 10% (P < 0.001). BMP-2 was entirely inhibitory (maximum inhibition of 7% at 5 nM, P < 0.0004). In an in vitro model for branching morphogenesis utilizing the kidney epithelial cell line, mIMCD-3, low doses of OP-1 (< 0.5 nM) increased the number of tubular structures formed by 28 +/- 5% (P = 0.01), whereas concentrations > 0.5 nM decreased that number by 22 +/- 8% (P = 0.02). All concentrations of BMP-2 (0.05-10 nM) were inhibitory (maximum inhibition at 10 nM of 88 +/- 3%, P < 0.0001). Stimulatory doses of OP-1 increased tubular length (P = 0.003) and the number of branch points/structure (3.2-fold increase, P = 0.0005) compared with BMP-2. To determine the molecular basis for these effects, we demonstrated th...Continue Reading

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Citations

Nov 21, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·K GeorgasM H Little
Aug 29, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Keith AlvaresArthur Veis
Jan 5, 2012·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·John K McGuireHelen Liapis
Sep 29, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nhue DoSeth J Karp
Jan 3, 2001·American Journal of Physiology. Renal Physiology·T D PiscioneN D Rosenblum
Aug 15, 2002·American Journal of Physiology. Cell Physiology·Kenzo NakamuraPaul B McCray
Nov 26, 2003·Hypertension·Pietro Amedeo ModestiGian Franco Gensini
Dec 25, 2009·American Journal of Physiology. Renal Physiology·Renfang SongIhor V Yosypiv
Feb 8, 2003·Stroke; a Journal of Cerebral Circulation·Chen-Fu ChangYun Wang
Jul 23, 2005·Circulation Research·Keith A HruskaGeorges Saab
Jul 22, 2011·American Journal of Physiology. Renal Physiology·Nicholas HaddadIndra R Gupta
Mar 27, 2003·American Journal of Physiology. Renal Physiology·Igor V Iosipiv, Mercedes Schroeder
Dec 24, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Michael Zeisberg
Feb 23, 2008·American Journal of Respiratory and Critical Care Medicine·Harsha H KariyawasamDouglas S Robinson
Apr 16, 2005·Molecular and Cellular Biology·Chungyee Leung-HagesteijnGregory E Hannigan
Jan 11, 2002·Developmental Biology·E M Ball, G P Risbridger
Feb 22, 2001·Developmental Biology·S GrisaruN D Rosenblum
Mar 17, 2004·Development·Mita M ShahSanjay K Nigam

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