Gene Symbol: Thbs4
Description: thrombospondin 4
Alias: TSP4, thrombospondin-4
Species: mouse
Products:     Thbs4

Top Publications

  1. Frolova E, Pluskota E, Krukovets I, Burke T, Drumm C, Smith J, et al. Thrombospondin-4 regulates vascular inflammation and atherogenesis. Circ Res. 2010;107:1313-25 pubmed publisher
    ..However, a role for TSP-4 in vascular wall biology remains unknown. We have examined the effects of TSP-4 gene (Thbs4) knockout on the development of atherosclerotic lesions in ApoE(-/-) mice...
  2. Posey K, Hankenson K, Veerisetty A, Bornstein P, Lawler J, Hecht J. Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1, thrombospondin-3, thrombospondin-5, and type IX collagen. Am J Pathol. 2008;172:1664-74 pubmed publisher
  3. Girard F, Eichenberger S, Celio M. Thrombospondin 4 deficiency in mouse impairs neuronal migration in the early postnatal and adult brain. Mol Cell Neurosci. 2014;61:176-86 pubmed publisher
    ..We focused our attention on Thrombospondin 4 (Thbs4), one of the 5 members of the Thrombospondin family of large, multidomain, extracellular matrix ..
  4. Newton G, Weremowicz S, Morton C, Jenkins N, Gilbert D, Copeland N, et al. The thrombospondin-4 gene. Mamm Genome. 1999;10:1010-6 pubmed
    ..The presence of multiple E-box sequence motifs is consistent with thrombospondin-4 expression in muscle and bone tissue. ..
  5. Pan B, Guo Y, Wu H, Park J, Trinh V, Luo Z, et al. Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury. Pain. 2016;157:2068-80 pubmed publisher
    ..Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury...
  6. Park J, Yu Y, Zhou C, Li K, Wang D, Chang E, et al. Central Mechanisms Mediating Thrombospondin-4-induced Pain States. J Biol Chem. 2016;291:13335-48 pubmed publisher
    Peripheral nerve injury induces increased expression of thrombospondin-4 (TSP4) in spinal cord and dorsal root ganglia that contributes to neuropathic pain states through unknown mechanisms...
  7. Lynch J, Maillet M, Vanhoutte D, Schloemer A, Sargent M, Blair N, et al. A thrombospondin-dependent pathway for a protective ER stress response. Cell. 2012;149:1257-68 pubmed publisher
    ..Here we describe a function for Thbs as ER-resident effectors of an adaptive ER stress response. Thbs4 cardiac-specific transgenic mice were protected from myocardial injury, whereas Thbs4(-/-) mice were sensitized to ..
  8. Li J, Willingham E, Baskin L. Gene expression profiles in mouse urethral development. BJU Int. 2006;98:880-5 pubmed
    ..b>TSP4 was expressed in the mesenchymal basal layer underlying E17 GT skin epidermis...
  9. Zhao Q, Beck A, Vitale J, Schneider J, Gao S, Chang C, et al. Developmental ablation of Id1 and Id3 genes in the vasculature leads to postnatal cardiac phenotypes. Dev Biol. 2011;349:53-64 pubmed publisher
    ..These findings provide important insights into the role/s of the endocardial network of the endothelial lineage in the development of cardiac disease, and highlight IGFbp3 as a potential link between Id and its vascular effectors. ..

More Information


  1. Frolova E, Sopko N, Blech L, Popovic Z, Li J, Vasanji A, et al. Thrombospondin-4 regulates fibrosis and remodeling of the myocardium in response to pressure overload. FASEB J. 2012;26:2363-73 pubmed publisher
    ..The aim of this study was to address the function of TSP-4 in the heart. TSP-4-knockout (Thbs4(-/-)) and wild-type (WT) mice were subjected to transverse aortic constriction (TAC) to increase left ventricle ..
  2. Zhou Z, Chen Y, Wang F, Tian N, Fan C. Effect of curcumin on down-expression of thrombospondin-4 induced by oxidized low-density lipoprotein in mouse macrophages. Biomed Mater Eng. 2014;24:181-9 pubmed publisher
    ..Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin. ..
  3. Benner E, Luciano D, Jo R, Abdi K, Paez Gonzalez P, Sheng H, et al. Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature. 2013;497:369-73 pubmed publisher
    ..Here we show in mice that SVZ-generated astrocytes express high levels of thrombospondin 4 (Thbs4), a secreted homopentameric glycoprotein, in contrast to cortical astrocytes, which express low levels ..
  4. Contreras Ruiz L, Regenfuss B, Mir F, Kearns J, Masli S. Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sjögren's syndrome. PLoS ONE. 2013;8:e75937 pubmed publisher
    ..These results not only reveal potential immunopathogenic mechanisms underlying KCS in SS but also highlight the therapeutic potential of TSP-1. ..
  5. Brody M, Schips T, Vanhoutte D, Kanisicak O, Karch J, Maliken B, et al. Dissection of Thrombospondin-4 Domains Involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling. Mol Cell Biol. 2016;36:2-12 pubmed publisher
    ..We recently reported that thrombospondin-4 (Thbs4) has a critical intracellular function, regulating the adaptive endoplasmic reticulum (ER) stress pathway through ..
  6. Baumeister A, Arber S, Caroni P. Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis. J Cell Biol. 1997;139:1231-42 pubmed
  7. Kim D, Li K, Boroujerdi A, Peter Yu Y, Zhou C, Deng P, et al. Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states. J Neurosci. 2012;32:8977-87 pubmed publisher
    ..pain development, we report here the characterization of a novel neuropathic pain contributor, thrombospondin-4 (TSP4), using a neuropathic pain model of spinal nerve ligation injury...
  8. Dunkle E, Zaucke F, Clegg D. Thrombospondin-4 and matrix three-dimensionality in axon outgrowth and adhesion in the developing retina. Exp Eye Res. 2007;84:707-17 pubmed
    ..These results support a model where TSP-4 acts as an organizer of adhesive and axon outgrowth-promoting molecules in the ECM to optimize retinal ganglion cell responses. ..
  9. Mendus D, Sundaresan S, Grillet N, Wangsawihardja F, Leu R, Muller U, et al. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. Eur J Neurosci. 2014;39:1256-67 pubmed publisher
    ..On the basis of the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear. ..
  10. Sawaki D, Hou L, Tomida S, Sun J, Zhan H, Aizawa K, et al. Modulation of cardiac fibrosis by Krüppel-like factor 6 through transcriptional control of thrombospondin 4 in cardiomyocytes. Cardiovasc Res. 2015;107:420-30 pubmed publisher
    ..Microarray analysis revealed increased levels of the extracellular matrix factor, thrombospondin 4 (TSP4), in the Klf6-ablated heart...
  11. Muppala S, Frolova E, Xiao R, Krukovets I, Yoon S, Hoppe G, et al. Proangiogenic Properties of Thrombospondin-4. Arterioscler Thromb Vasc Biol. 2015;35:1975-86 pubmed publisher angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using Thbs4(-/-) mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4...
  12. Lv L, Liang W, Ye M, Zhang J, Zhang H, Xue G, et al. Thrombospondin-4 ablation reduces macrophage recruitment in adipose tissue and neointima and suppresses injury-induced restenosis in mice. Atherosclerosis. 2016;247:70-7 pubmed publisher
    Thrombospondin-4 (Thbs4) is a member of the extracellular calcium-binding protein family and is linked to cell adhesion and migration...
  13. Arber S, Ladle D, Lin J, Frank E, Jessell T. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell. 2000;101:485-98 pubmed
    ..ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord. ..
  14. Vanhoutte D, Schips T, Kwong J, Davis J, Tjondrokoesoemo A, Brody M, et al. Thrombospondin expression in myofibers stabilizes muscle membranes. elife. 2016;5: pubmed publisher
    ..Here we show that Thrombospondin-4 (Thbs4) regulates skeletal muscle integrity and its susceptibility to muscular dystrophy through organization of membrane ..
  15. Cingolani O, Kirk J, Seo K, Koitabashi N, Lee D, Ramirez Correa G, et al. Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle. Circ Res. 2011;109:1410-4 pubmed publisher
    ..Because levels of the matricellular protein thrombospondin-4 (TSP4) rapidly rise in hypertension and are elevated in cardiac stress overload and heart failure, we hypothesized that ..
  16. Havis E, Bonnin M, Olivera Martinez I, Nazaret N, Ruggiu M, Weibel J, et al. Transcriptomic analysis of mouse limb tendon cells during development. Development. 2014;141:3683-96 pubmed publisher
    ..FGF does not have a tenogenic effect and the inhibition of the ERK MAPK signalling pathway was sufficient to activate Scx in mouse limb mesodermal progenitors and mesenchymal stem cells. ..
  17. Margagliotti S, Clotman F, Pierreux C, Beaudry J, Jacquemin P, Rousseau G, et al. The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. Dev Biol. 2007;311:579-89 pubmed
    ..This network operating at the onset of liver development contains candidate genes for investigation of liver carcinogenesis. ..
  18. Frolova E, Drazba J, Krukovets I, Kostenko V, Blech L, Harry C, et al. Control of organization and function of muscle and tendon by thrombospondin-4. Matrix Biol. 2014;37:35-48 pubmed publisher
    ..In Thbs4(-/-) mice, tendon collagen fibrils are significantly larger than in wild-type mice, and there is no compensatory ..
  19. Palao T, Rippe C, van Veen H, Vanbavel E, Swärd K, Bakker E. Thrombospondin-4 knockout in hypertension protects small-artery endothelial function but induces aortic aneurysms. Am J Physiol Heart Circ Physiol. 2016;310:H1486-93 pubmed publisher
    ..In this study, we explored the role of TSP-4 in hypertension. For this purpose, wild-type and TSP-4 knockout (Thbs4(-/-)) mice were treated with angiotensin II (ANG II)...