Tumors associated with osteomalacia elaborate the novel factor(s), phosphatonin(s), which causes phosphaturia and hypophosphatemia by cAMP-independent pathways. We show that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, is a circulating phosphaturic factor that antagonizes renal Wnt-signaling. In cultured opossum renal epithelial cells, sFRP-4 specific...

Secreted frizzled related proteins (sFRP) are regulators of Wnt signaling pathways that play central roles in developmental processes and oncogenesis. Various sFRP genes have been cloned from different tissues and implicated in diverse biological activities. rFrp, the rat homologue of sFRP-4, was initially identified as being upregulated in mutant p53-induced cellular transformation. Here, we r...

The canonical Wnt signalling pathway plays a key role during embryogenesis and pathogenesis of various types of tumors. Recently, several studies have shown that the promoter hypermethylation of Wnt-antagonist genes, including sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wif-1 and Dkk-3, have been certified to contribute to the tumorigenesis of several cancers. The aim of this study was to investigate the p...

BACKGROUND sFRP-3 is a soluble antagonist of Wnts, widely expressed in developing embryos. The Wnt gene family comprises cysteine-rich secreted ligands that regulate cell proliferation, differentiation, organogenesis and oncogenesis of different organisms ranging from worms to mammals. In the canonical signal transduction pathway Wnt proteins bind to the extracellular domain of Frizzled recepto...

BACKGROUND The Wnt/β-catenin signaling pathway plays a central role during cardiac development and has been implicated in cardiac remodeling and aging. However, the role of Wnt modulators in this process is unknown. In this study, we examined the role of the Wnt signaling inhibitor secreted frizzled-related protein-1 (sFRP-1) in aged wild-type and sFRP-1-deficient mice. METHODS AND RESULTS sF...

Wnt signaling regulates a wide range of developmental processes such as proliferation, cell migration, axon guidance, and cell fate determination. In this report, we studied the expression of secreted frizzled related protein-2 (SFRP-2), which codes for a putative Wnt inhibitor, in the developing nervous system. SFRP-2 is expressed in several discrete neuroepithelial domains, including the dien...

In diabetics, methylglyoxal (MG), a glucose-derived metabolite, plays a noxious role by inducing oxidative stress, which causes and exacerbates a series of complications including low-turnover osteoporosis. In the present study, while MG treatment of mouse bone marrow stroma-derived ST2 cells rapidly suppressed the expression of osteotrophic Wnt-targeted genes, including that of osteoprotegerin...

Background: A major goal of the Target Enablement to Accelerate Therapy Development for Alzheimer’s disease (TREAT-AD) program is develop and identify high-quality tools test target or mechanistic hypotheses. As part this initiative, it important that commercial reagents including research antibodies being used interrogate drug targets have confirmed validation data ...