Gene Symbol: Itgb6
Description: integrin beta 6
Alias: 2210409C20Rik, 4831415H04Rik, integrin beta-6
Species: mouse
Products:     Itgb6

Top Publications

  1. Yang Z, Mu Z, Dabovic B, Jurukovski V, Yu D, Sung J, et al. Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol. 2007;176:787-93 pubmed
    ..These findings indicate that RGD-binding integrins are requisite latent TGFbeta1 activators during development and in the immune system. ..
  2. Huang X, Wu J, Cass D, Erle D, Corry D, Young S, et al. Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin. J Cell Biol. 1996;133:921-8 pubmed
    ..Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin. ..
  3. Mohazab L, Koivisto L, Jiang G, Kytomaki L, Haapasalo M, Owen G, et al. Critical role for ?v?6 integrin in enamel biomineralization. J Cell Sci. 2013;126:732-44 pubmed publisher
    ..Human and mouse ameloblasts were found to express both ?6 integrin mRNA and protein. The maxillary incisors of Itgb6(-/-) mice lacked yellow pigment and their mandibular incisors appeared chalky and rounded...
  4. Aluwihare P, Mu Z, Zhao Z, Yu D, Weinreb P, Horan G, et al. Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice. J Cell Sci. 2009;122:227-32 pubmed publisher
    ..Most Itgb6-/-;Itgb8-/- embryos die at mid-gestation; those that survive develop cleft palate-as observed in Tgfb3-/- mice...
  5. Hahm K, Lukashev M, Luo Y, Yang W, Dolinski B, Weinreb P, et al. Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse. Am J Pathol. 2007;170:110-25 pubmed
    ..These findings demonstrate that alpha v beta6 can contribute to the regulation of renal fibrosis and suggest this integrin as a potential therapeutic target. ..
  6. Morris D, Huang X, Kaminski N, Wang Y, Shapiro S, Dolganov G, et al. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature. 2003;422:169-73 pubmed
    ..Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that ..
  7. Ghannad F, Nica D, Fulle M, Grenier D, Putnins E, Johnston S, et al. Absence of alphavbeta6 integrin is linked to initiation and progression of periodontal disease. Am J Pathol. 2008;172:1271-86 pubmed publisher
    ..Thus, alphavbeta6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-beta1. ..
  8. Xie Y, McElwee K, Owen G, Hakkinen L, Larjava H. Integrin ?6-deficient mice show enhanced keratinocyte proliferation and retarded hair follicle regression after depilation. J Invest Dermatol. 2012;132:547-55 pubmed publisher
    ..Thus, downregulated TGF-?1 signaling in ?6(-/-) mice may affect bulge niche stem cell behavior. ..
  9. Ma L, Yang H, Gaspert A, Carlesso G, Barty M, Davidson J, et al. Transforming growth factor-beta-dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice. Am J Pathol. 2003;163:1261-73 pubmed

Scientific Experts

More Information


  1. Ludlow A, Yee K, Lipman R, Bronson R, Weinreb P, Huang X, et al. Characterization of integrin beta6 and thrombospondin-1 double-null mice. J Cell Mol Med. 2005;9:421-37 pubmed
    ..They also indicate that alphavbeta6 functions as a tumor suppressor gene and that activation of TGFbeta by TSP-1 and alphavbeta6 contributes to normal tissue architecture and function...
  2. Mollah M, Ishikawa A. Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight. Mamm Genome. 2011;22:282-9 pubmed publisher
    ..These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci. ..
  3. Huang X, Wu J, Zhu W, Pytela R, Sheppard D. Expression of the human integrin beta6 subunit in alveolar type II cells and bronchiolar epithelial cells reverses lung inflammation in beta6 knockout mice. Am J Respir Cell Mol Biol. 1998;19:636-42 pubmed
  4. Blanco Mezquita J, Hutcheon A, Stepp M, Zieske J. ?V?6 integrin promotes corneal wound healing. Invest Ophthalmol Vis Sci. 2011;52:8505-13 pubmed publisher
    ..It is hypothesized that the lack of ?v?6 leads to reduced laminin production during wound repair. This lack of laminin prevents reassembly of the BMZ and mature hemidesmosomes after keratectomy in ?6(-/-) mice. ..
  5. Poulter J, Brookes S, Shore R, Smith C, Abi Farraj L, Kirkham J, et al. A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta. Hum Mol Genet. 2014;23:2189-97 pubmed publisher
    ..Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I-domain of integrin-?6 (ITGB6), which is consistently predicted to be pathogenic by all available programmes and is the only variant that ..
  6. Sugimoto K, Kudo M, Sundaram A, Ren X, Huang K, Bernstein X, et al. The ?v?6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012;122:748-58 pubmed publisher
  7. Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman S, Schuppan D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology. 2008;135:660-70 pubmed publisher
    ..Because its role in liver fibrosis is unknown, we studied alphavbeta6 function in vitro and explored the antifibrotic potential of the specific alphavbeta6 antagonist EMD527040...
  8. Wang S, Choi M, Richardson A, Reid B, Lin B, Wang S, et al. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta. Hum Mol Genet. 2014;23:2157-63 pubmed publisher
    ..Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations...
  9. Puthawala K, Hadjiangelis N, Jacoby S, Bayongan E, Zhao Z, Yang Z, et al. Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med. 2008;177:82-90 pubmed
    ..Wild-type mice, alpha(v)beta6-deficient (Itgb6-/-) mice, and mice heterozygous for a Tgfb1 mutation that eliminates integrin-mediated activation (Tgfb1(+/RGE)) ..
  10. Ding X, Wang X, Zhao X, Jin S, Tong Y, Ren H, et al. RGD peptides protects against acute lung injury in septic mice through Wisp1-integrin β6 pathway inhibition. Shock. 2015;43:352-60 pubmed publisher
    ..These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin β6 pathway. ..
  11. AlDahlawi S, Eslami A, Hakkinen L, Larjava H. The alphavbeta6 integrin plays a role in compromised epidermal wound healing. Wound Repair Regen. 2006;14:289-97 pubmed
    ..The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone. ..
  12. Jenkins R, Su X, Su G, Scotton C, Camerer E, Laurent G, et al. Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury. J Clin Invest. 2006;116:1606-14 pubmed
    ..ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6-/- mice. Furthermore, Itgb6-/- mice are also protected from ventilator-induced lung edema...
  13. Fontana L, Chen Y, Prijatelj P, Sakai T, Fassler R, Sakai L, et al. Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J. 2005;19:1798-808 pubmed
    ..The results indicate specificity for integrin-mediated latent TGF-beta activation that include unique sequences in LTBP-1 and an appropriate matrix molecule. ..
  14. Kaminski N, Allard J, Pittet J, Zuo F, Griffiths M, Morris D, et al. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci U S A. 2000;97:1778-83 pubmed
    ..The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs. ..
  15. Moriya K, Bae E, Honda K, Sakai K, Sakaguchi T, Tsujimoto I, et al. A fibronectin-independent mechanism of collagen fibrillogenesis in adult liver remodeling. Gastroenterology. 2011;140:1653-63 pubmed publisher
    ..Transforming growth factor-? and type V collagen are targets for regulating the initial fibrogenic response to liver damage. ..
  16. Wu X, Liao Y, Wang H, Ji K, Li G, Zang B. Integrin alphavbeta6 is involved in measles protein-induced airway immune suppression. Cytokine. 2012;59:59-64 pubmed publisher
    ..Activation of MVP-induced Tregs powerfully suppressed polarized CD4(+) T cells. Exposure to MVP can induce Treg development in the lung that plays an important role in the suppression of CD4(+) T cell function. ..
  17. Geng H, Lan R, Singha P, Gilchrist A, Weinreb P, Violette S, et al. Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and G?q-mediated Rho and ?v?6 integrin-dependent activation of TGF-?. Am J Pathol. 2012;181:1236-49 pubmed publisher
    ..We suggest that LPA-initiated autocrine signaling is a potentially important mechanism that gives rise to paracrine profibrotic signaling in injured kidney tubule cells. ..
  18. Rognoni E, Widmaier M, Jakobson M, Ruppert R, Ussar S, Katsougkri D, et al. Kindlin-1 controls Wnt and TGF-? availability to regulate cutaneous stem cell proliferation. Nat Med. 2014;20:350-9 pubmed publisher
    ..Our findings assign Kindlin-1 the previously unknown and essential task of controlling cutaneous epithelial stem cell homeostasis by balancing TGF-?-mediated growth-inhibitory signals and Wnt-?-catenin-mediated growth-promoting signals. ..
  19. Chaen T, Konno T, Egashira M, Bai R, Nomura N, Nomura S, et al. Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion competence. PLoS ONE. 2012;7:e48933 pubmed publisher
    ..These findings define for the first time specific regulatory components of an estrogen-dependent pathway coordinating blastocyst adhesion competence and uterine receptivity...
  20. Ducceschi M, Clifton L, Stimpson S, Billin A. Post-transcriptional regulation of ITGB6 protein levels in damaged skeletal muscle. J Mol Histol. 2014;45:329-36 pubmed publisher
    We have identified integrin beta 6 (Itgb6) as a transcript highly enriched in skeletal muscle. This finding is unexpected because Itgb6 is typically associated with epithelial expression domains in normal tissue...
  21. Chan C, Weeber E, Kurup S, Sweatt J, Davis R. Integrin requirement for hippocampal synaptic plasticity and spatial memory. J Neurosci. 2003;23:7107-16 pubmed
    ..These results demonstrate that several different integrins are involved in physiological plasticity and provide the first evidence of their requirement for behavioral plasticity in vertebrates. ..
  22. Mohammed J, Beura L, Bobr A, Astry B, Chicoine B, Kashem S, et al. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β. Nat Immunol. 2016;17:414-21 pubmed publisher
    ..Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication. ..
  23. Arend L, Smart A, Briggs J. Mouse beta(6) integrin sequence, pattern of expression, and role in kidney development. J Am Soc Nephrol. 2000;11:2297-305 pubmed
    ..These findings suggest an important role for beta(6) integrin in normal development of the mouse kidney. ..
  24. Wada J, Kumar A, Liu Z, Ruoslahti E, Reichardt L, Marvaldi J, et al. Cloning of mouse integrin alphaV cDNA and role of the alphaV-related matrix receptors in metanephric development. J Cell Biol. 1996;132:1161-76 pubmed
    ..The expressions of integrin beta3, beta5, and beta6 were unaltered. These findings suggest that the integrin alphaV is developmentally regulated, has a distinct spatio-temporal expression, and is relevant in the mammalian organogenesis. ..
  25. Nik A, Johansson J, Ghiami M, Reyahi A, Carlsson P. Foxf2 is required for secondary palate development and Tgf? signaling in palatal shelf mesenchyme. Dev Biol. 2016;415:14-23 pubmed publisher
    ..We therefore propose that gene expression changes in palatal shelf mesenchyme that lead to reduced Tgf? signaling contribute to cleft palate in Foxf2(-)(/)(-) mice. ..
  26. Jolly L, Stavrou A, Vanderstoken G, Meliopoulos V, Habgood A, Tatler A, et al. Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation. J Biol Chem. 2014;289:35246-63 pubmed publisher
  27. Velsko I, Chukkapalli S, Rivera Kweh M, Zheng D, Aukhil I, Lucas A, et al. Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in αvβ6 integrin-deficient mice. Infect Immun. 2015;83:4582-93 pubmed publisher
    ..These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well-characterized periodontal pathogens. ..
  28. Hogmalm A, Sheppard D, Lappalainen U, Bry K. beta6 Integrin subunit deficiency alleviates lung injury in a mouse model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol. 2010;43:88-98 pubmed publisher
    ..We conclude that absence of the beta6 integrin subunit protects the infant murine lung against IL-1beta-induced inflammation and injury. ..
  29. Pittet J, Griffiths M, Geiser T, Kaminski N, Dalton S, Huang X, et al. TGF-beta is a critical mediator of acute lung injury. J Clin Invest. 2001;107:1537-44 pubmed
  30. Knight P, Wright S, Brown J, Huang X, Sheppard D, Miller H. Enteric expression of the integrin alpha(v)beta(6) is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1. Am J Pathol. 2002;161:771-9 pubmed
  31. Huang X, Wu J, Spong S, Sheppard D. The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin. J Cell Sci. 1998;111 ( Pt 15):2189-95 pubmed
  32. Popov Y, Patsenker E, Stickel F, Zaks J, Bhaskar K, Niedobitek G, et al. Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies. J Hepatol. 2008;48:453-64 pubmed publisher
    ..2) In vivo a single dose of a small molecule alphavbeta6 inhibitor induced antifibrogenic and profibrolytic genes and activities, suggesting alphavbeta6 is a unique target for treatment of liver fibrosis. ..
  33. Yang G, Xu K, Pan Z, Zhang Z, Mi Y, Wang J, et al. Integrin alpha v beta 6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver. Cancer Sci. 2008;99:879-87 pubmed publisher
    ..The mechanisms that alpha v beta 6 may be involved in include the promotion of MMP-9 secretion, the enhancement of migration on fibronectin, and the survival of cancer cells in the liver. ..
  34. Baudoin C, Goumans M, Mummery C, Sonnenberg A. Knockout and knockin of the beta1 exon D define distinct roles for integrin splice variants in heart function and embryonic development. Genes Dev. 1998;12:1202-16 pubmed
    ..We propose that beta1D is less efficient than beta1A in mediating the signaling that regulates cell motility and responses of the cells to mechanical stress. ..
  35. Henderson N, Arnold T, Katamura Y, Giacomini M, Rodriguez J, McCarty J, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19:1617-24 pubmed publisher
    ..These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all α(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases. ..
  36. Mukhametshina R, Ruhs A, Singh I, Hasan D, Contreras A, Mehta A, et al. Quantitative proteome analysis of alveolar type-II cells reveals a connection of integrin receptor subunits beta 2/6 and WNT signaling. J Proteome Res. 2013;12:5598-608 pubmed publisher
    ..Interestingly, we confirmed our data for two of these genes, integrin beta 2 and 6 (Itgb2 and Itgb6), by qRT-PCR expression analysis and Western blot analysis of protein extracts...
  37. Kim H, Ryu J, Woo H, Cho S, Sung M, Kim S, et al. Patterns of gene expression associated with Pten deficiency in the developing inner ear. PLoS ONE. 2014;9:e97544 pubmed publisher
    ..From this study, we suggest two key regulatory signaling networks mediated by Spp1 and Rgs4, which may play potential roles in neuronal differentiation of developing auditory neurons. ..
  38. Koth L, Alex B, Hawgood S, Nead M, Sheppard D, Erle D, et al. Integrin beta6 mediates phospholipid and collectin homeostasis by activation of latent TGF-beta1. Am J Respir Cell Mol Biol. 2007;37:651-9 pubmed
    ..Adult mice lacking the beta-subunit of alphavbeta6 (Itgb6-/-) developed increased bronchoalveolar lavage phospholipids and surfactant proteins A and D, and demonstrated ..
  39. Wang J, Bao L, Yu B, Liu Z, Han W, Deng C, et al. Interleukin-1β Promotes Epithelial-Derived Alveolar Elastogenesis via αvβ6 Integrin-Dependent TGF-β Activation. Cell Physiol Biochem. 2015;36:2198-216 pubmed publisher
  40. Blanpain C, Lowry W, Pasolli H, Fuchs E. Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev. 2006;20:3022-35 pubmed
  41. Tatler A, Habgood A, Porte J, John A, Stavrou A, Hodge E, et al. Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin αvβ6 Expression. J Biol Chem. 2016;291:9540-53 pubmed publisher
    ..Here we identify a region in the β6 subunit gene (ITGB6) promoter acting to markedly repress basal gene transcription, which responds to both the Ets domain-containing ..
  42. Xu K, Nieuwenhuis E, Cohen B, Wang W, Canty A, Danska J, et al. Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol. 2010;298:L45-56 pubmed publisher
    ..In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation. ..
  43. Song Y, Pittet J, Huang X, He H, Lynch S, Violette S, et al. Role of integrin alphav beta6 in acute lung injury induced by Pseudomonas aeruginosa. Infect Immun. 2008;76:2325-32 pubmed publisher
    ..aeruginosa-induced lung injury. However, these therapies also did not increase the lung injury, suggesting that host defense was not compromised by this promising new therapy. ..
  44. Knight P, Brown J, Wright S, Thornton E, Pate J, Miller H. Aberrant mucosal mast cell protease expression in the enteric epithelium of nematode-infected mice lacking the integrin alphavbeta6, a transforming growth factor-beta1 activator. Am J Pathol. 2007;171:1237-48 pubmed
  45. Ishikawa A, Okuno S. Fine mapping and candidate gene search of quantitative trait loci for growth and obesity using mouse intersubspecific subcongenic intercrosses and exome sequencing. PLoS ONE. 2014;9:e113233 pubmed publisher
    ..12 and that Ly75 and Itgb6 are putative candidate genes for Pbwg1.5...
  46. Xie Y, Gao K, Hakkinen L, Larjava H. Mice lacking beta6 integrin in skin show accelerated wound repair in dexamethasone impaired wound healing model. Wound Repair Regen. 2009;17:326-39 pubmed publisher
    ..Inhibition of alphavbeta6 integrin may provide a future target for treatment of impaired wound healing. ..