Disease relevance of Sfrp4

• Furthermore, recombinant sFRP4 reduced the number of myofibroblasts, a central mediator of fibrosis [1].
• These predictions were tested by determination of the expression and function of an inhibitor of Wnt signaling, secreted frizzled-related protein 4 (sFRP4), during renal tubular epithelial injury initiated by unilateral ureteral obstruction (UUO) [1].
• New insights into phosphate homeostasis: fibroblast growth factor 23 and frizzled-related protein-4 are phosphaturic factors derived from tumors associated with osteomalacia [2].

High impact information on Sfrp4

• The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23 [3].
• Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3 [4].
• Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution [4].
• The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4 [4].
• Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution [4].

Biological context of Sfrp4

• Conclusions: In SAMP6 mice, Sfrp4 negatively regulates bone formation and decreases BMD through the inhibition of Wnt signaling [5].
• Despite increased sFRP4 gene expression in perivascular regions of injured kidneys, total sFRP4 protein levels decreased after injury [1].
• Cloning and characterization of the promoter region of the mouse frizzled-related protein 4 gene [6].

Anatomical context of Sfrp4

• The levels of expression of all genes in the segregated interval were examined, and we clarified the effect of the candidate gene, secreted frizzled-related protein (Sfrp4), on osteoblasts in vitro [5].
• Quantitative RT-PCR analysis of calvaria tissue showed approximately 40-fold higher levels of expression of Sfrp4 in SAMP6 than in P6.P2-13 [5].
• While sFRP1 is specifically expressed in the embryonic metanephros, eye, brain, teeth, salivary gland and small intestine, there is only weak expression of sFRP4 except for the developing teeth, eye and salivary gland [7].
• It is concluded that beta-catenin signaling is activated in tubular epithelial and interstitial cells after renal injury, and recombinant sFRP4 can interfere with epithelial de-differentiation and with fibroblast differentiation and function during progression of renal fibrosis [1].
• We observed that Msx-1, Wnt4, and a Wnt antagonist sFRP4 are differentially expressed in the mouse uterus during the periimplantation period, suggesting their role in implantation [8].

Associations of Sfrp4 with chemical compounds

• The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1alpha,25-dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and further reduction in phosphate retention by the organism [9].

Other interactions of Sfrp4

• The decreased sFRP4 protein levels after UUO accompanied increased Wnt-dependent beta-catenin signaling in tubular epithelial and interstitial cells, along with increased expression of markers of fibrosis [1].
• Moreover, antagonists of Wnt signaling, sFRP1, sFRP2, and sFRP4 (secreted frizzled-related proteins) were significantly up-regulated, suggesting active inhibition of the Wnt pathway [10].

Analytical, diagnostic and therapeutic context of Sfrp4

• In this study the promoter region of mouse frizzled related protein 4 (sFrp4) gene was cloned, sequenced, and analyzed using transient reporter assays along with site-directed mutagenesis [6].

References