Gene Symbol: Sfrp4
Description: secreted frizzled-related protein 4
Alias: secreted frizzled-related sequence protein 4, FRP-4, frizzled-related protein 4, sFRP-4
Species: mouse
Products:     Sfrp4

Top Publications

  1. Nakanishi R, Shimizu M, Mori M, Akiyama H, Okudaira S, Otsuki B, et al. Secreted frizzled-related protein 4 is a negative regulator of peak BMD in SAMP6 mice. J Bone Miner Res. 2006;21:1713-21 pubmed
    ..b>Sfrp 4 within this locus was responsible for lower BMD of SAMP6...
  2. Wong V, Yam J, Hsiao W. Cloning and characterization of the promoter region of the mouse frizzled-related protein 4 gene. Biol Chem. 2003;384:1147-54 pubmed
    ..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-..
  3. Wawrzak D, Metioui M, Willems E, Hendrickx M, De Genst E, Leyns L. Wnt3a binds to several sFRPs in the nanomolar range. Biochem Biophys Res Commun. 2007;357:1119-23 pubmed
    ..Here we show, using surface plasmon resonance and purified proteins, that sFRP1, sFRP2, sFRP4, and Frzb bind directly to Wnt3a with affinities in the nanomolar range...
  4. Yam J, Chan K, Wong V, Hsiao W. Transcriptional activity of the promoter region of rat frizzled-related protein gene. Biochem Biophys Res Commun. 2001;286:94-100 pubmed
    ..This work provides a transcriptional regulation basis for Frp and gives insight into its implication in tumorigenesis. ..
  5. Chen C, Murray P, Jiang T, Plikus M, Chang Y, Lee O, et al. Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4. J Invest Dermatol. 2014;134:2086-2096 pubmed publisher
    ..Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen...
  6. Cho H, Choi H, Sun H, Yang J, An J, Cho S, et al. Transgenic mice overexpressing secreted frizzled-related proteins (sFRP)4 under the control of serum amyloid P promoter exhibit low bone mass but did not result in disturbed phosphate homeostasis. Bone. 2010;47:263-71 pubmed publisher
    Secreted frizzled-related protein-4 (sFRP4) is a member of secreted modulators of Wnt signaling pathways and has been recognized to play important role in the pathogenesis of oncogenic osteomalacia as a potential phosphatonin...
  7. Huyghe A, Van den Ackerveken P, Sacheli R, Prévot P, Thelen N, Renauld J, et al. MicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5. Cell Rep. 2015;13:31-42 pubmed publisher
    ..By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also ..
  8. Kiper P, Saito H, Gori F, Unger S, Hesse E, Yamana K, et al. Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. N Engl J Med. 2016;374:2553-2562 pubmed publisher
    ..In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor...
  9. Surendran K, Schiavi S, Hruska K. Wnt-dependent beta-catenin signaling is activated after unilateral ureteral obstruction, and recombinant secreted frizzled-related protein 4 alters the progression of renal fibrosis. J Am Soc Nephrol. 2005;16:2373-84 pubmed
    ..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)...

More Information


  1. Martin N, Jaubert J, Glaser P, Szatanik M, Guenet J. Genetic and physical delineation of the region overlapping the progressive motor neuropathy (pmn) locus on mouse chromosome 13. Genomics. 2001;75:9-16 pubmed
  2. Haraguchi R, Kitazawa R, Mori K, Tachibana R, Kiyonari H, Imai Y, et al. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss. Sci Rep. 2016;6:25198 pubmed publisher
    b>sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts...
  3. Chang J, Esumi N, Moore K, Li Y, Zhang S, Chew C, et al. Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium. Hum Mol Genet. 1999;8:575-83 pubmed
    ..1; human SFRP2 maps to 4q31.3. Based on the biology and complementary expression patterns of SFRP2 and SFRP5, we suggest that they may be involved in determining the polarity of photoreceptor, and perhaps other, cells in the retina. ..
  4. Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, et al. Diabetic osteopenia by decreased ?-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene. PLoS ONE. 2014;9:e102797 pubmed publisher
  5. Keil K, Mehta V, Branam A, Abler L, Buresh Stiemke R, Joshi P, et al. Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development. Endocrinology. 2012;153:6091-103 pubmed publisher
  6. Tian Y, Wang W, Lu Q, Chen P, Ma K, Jia Z, et al. Cross-talk of SFRP4, integrin ?1?1, and Notch1 inhibits cardiac differentiation of P19CL6 cells. Cell Signal. 2016;28:1806-15 pubmed publisher
    Signaling pathways play an important role in cardiogenesis. Secreted frizzled-related protein 4 (SFRP4), a member of the Wnt family, contributes to adipogenesis and tumorigenesis...
  7. Mastaitis J, Eckersdorff M, Min S, Xin Y, Cavino K, Aglione J, et al. Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice. Endocrinology. 2015;156:4502-10 pubmed publisher
    Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway...
  8. Leimeister C, Bach A, Gessler M. Developmental expression patterns of mouse sFRP genes encoding members of the secreted frizzled related protein family. Mech Dev. 1998;75:29-42 pubmed
    ..In a comparative analysis transcripts of the related sFRP1 and sFRP4 genes were frequently found in the same tissues as sFRP2 with their expression domains overlapping in some ..
  9. Constantinou T, Baumann F, Lacher M, Saurer S, Friis R, Dharmarajan A. SFRP-4 abrogates Wnt-3a-induced beta-catenin and Akt/PKB signalling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation. J Mol Signal. 2008;3:10 pubmed publisher
    ..All these behavioural changes can be blocked in mammary epithelial cells expressing SFRP-4. Thus, our data illustrate in an in vitro model a mechanism by which SFRP-4 can modulate a differentiation response to Wnt-3a. ..
  10. Bai J, Liu Z, Xu Z, Ke F, Zhang L, Zhu H, et al. Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis. J Immunol. 2015;194:4185-98 pubmed publisher
    ..b>SFRP4 directly inhibited excessive keratinocyte proliferation evoked by proinflammatory cytokines in vitro...
  11. Boudin E, Piters E, Fijalkowski I, Stevenheydens G, Steenackers E, Kuismin O, et al. Mutations in sFRP1 or sFRP4 are not a common cause of craniotubular hyperostosis. Bone. 2013;52:292-5 pubmed publisher
    ..Studies using mice showed that two members of this family, sFRP1 and sFRP4, have an important effect on bone formation...
  12. Mishra S, Choe Y, Pleasure S, Siegenthaler J. Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF-A pathways downstream of retinoic acid from the meninges. Dev Biol. 2016;420:148-165 pubmed publisher
    ..Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations. ..
  13. Jin C, Chen J, Meng Q, Carreira V, Tam N, Geh E, et al. Deciphering gene expression program of MAP3K1 in mouse eyelid morphogenesis. Dev Biol. 2013;374:96-107 pubmed publisher
    ..Using LCM and expression array, our studies have uncovered novel molecular signatures of MAP3K1 in embryonic eyelid closure. ..
  14. Christov M, Koren S, Yuan Q, Baron R, Lanske B. Genetic ablation of sfrp4 in mice does not affect serum phosphate homeostasis. Endocrinology. 2011;152:2031-6 pubmed publisher
    ..In addition to Fgf23, secreted frizzled-related protein 4 (Sfrp4) has recently been implicated as an additional phosphate regulator in vivo and in vitro...
  15. Ikegawa M, Han H, Okamoto A, Matsui R, Tanaka M, Omi N, et al. Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice. Dev Dyn. 2008;237:2506-17 pubmed publisher
    ..Although joint formation was not disrupted, chondrocyte maturation was preaxially disturbed. Our results suggest that the Sfrp2 deleted mice can be a useful animal model to study human syndactyly/preaxial synpolydactyly defects...
  16. Cho S, Her S, Sun H, Choi O, Yang J, Kim S, et al. Differential effects of secreted frizzled-related proteins (sFRPs) on osteoblastic differentiation of mouse mesenchymal cells and apoptosis of osteoblasts. Biochem Biophys Res Commun. 2008;367:399-405 pubmed publisher
    ..In conclusion, we found that different repertoires of sFRPs exert differential effects on osteoblastic differentiation of mouse mesenchymal cells and cellular apoptosis of mouse osteoblasts in vitro. ..
  17. Bayle J, Fitch J, Jacobsen K, Kumar R, Lafyatis R, Lemaire R. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J Invest Dermatol. 2008;128:871-81 pubmed
    ..beta-catenin (DACT1) and DACT2; Wnt-induced secreted protein 2; and secreted frizzled-related protein (SFRP)2 and SFRP4. RNase protection and northern blot confirmed microarray results...
  18. Nakanishi R, Akiyama H, Kimura H, Otsuki B, Shimizu M, Tsuboyama T, et al. Osteoblast-targeted expression of Sfrp4 in mice results in low bone mass. J Bone Miner Res. 2008;23:271-7 pubmed
    Transgenic mice overexpressing Sfrp4 in osteoblasts were established. These mice exhibited low bone mass caused by a decrease in bone formation...
  19. Hsieh M, Mulders S, Friis R, Dharmarajan A, Richards J. Expression and localization of secreted frizzled-related protein-4 in the rodent ovary: evidence for selective up-regulation in luteinized granulosa cells. Endocrinology. 2003;144:4597-606 pubmed
    ..Therefore, regulation of sFRP-4 by LH and PRL may be important for modulating Fz-1, which is known to be expressed in periovulatory follicles, and Wnt-4/Fz-4, which are expressed in corpora lutea. ..
  20. Tebar M, Destree O, de Vree W, Ten Have Opbroek A. Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung. Mech Dev. 2001;109:437-40 pubmed
    ..5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-temporal patterns.
  21. Lee C, Buttitta L, May N, Kispert A, Fan C. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development. 2000;127:109-18 pubmed
    ..Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm. ..