Mfge8

Summary

Gene Symbol: Mfge8
Description: milk fat globule-EGF factor 8 protein
Alias: AA408458, AI325141, MFG-E8, MP47, Mfgm, P47, SED1, lactadherin, lactadherin, EGF/factor VIII, milk fat globule glycoprotein, sperm surface protein SP47
Species: mouse
Products:     Mfge8

Top Publications

  1. Miyasaka K, Hanayama R, Tanaka M, Nagata S. Expression of milk fat globule epidermal growth factor 8 in immature dendritic cells for engulfment of apoptotic cells. Eur J Immunol. 2004;34:1414-22 pubmed
    ..These results indicated that MFG-E8 plays an essential role in the engulfment of apoptotic cells by bone marrow-derived immature DC. ..
  2. Neutzner M, Lopez T, Feng X, Bergmann Leitner E, Leitner W, Udey M. MFG-E8/lactadherin promotes tumor growth in an angiogenesis-dependent transgenic mouse model of multistage carcinogenesis. Cancer Res. 2007;67:6777-85 pubmed
    ..MFG-E8 (also termed lactadherin) and developmental endothelial locus 1 (Del1) constitute a two-gene family of alpha(v)beta(3)/beta(5) ligands ..
  3. Yang C, Hayashida T, Forster N, Li C, Shen D, Maheswaran S, et al. The integrin alpha(v)beta(3-5) ligand MFG-E8 is a p63/p73 target gene in triple-negative breast cancers but exhibits suppressive functions in ER(+) and erbB2(+) breast cancers. Cancer Res. 2011;71:937-45 pubmed publisher
    ..Its potential use as a serum biomarker that contributes to the pathogenesis of triple-negative breast cancers urges continued evaluation of its differential functions. ..
  4. Neniskyte U, Brown G. Lactadherin/MFG-E8 is essential for microglia-mediated neuronal loss and phagoptosis induced by amyloid ?. J Neurochem. 2013;126:312-7 pubmed publisher
    ..We report here that this neuronal loss is mediated by the bridging protein lactadherin/milk-fat globule epidermal growth factor-like factor 8 (MFG-E8), which is released by A?-activated microglia, ..
  5. Aoki N, Ishii T, Ohira S, Yamaguchi Y, Negi M, Adachi T, et al. Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, beta-casein. Biochim Biophys Acta. 1997;1334:182-90 pubmed
    The expression of mouse milk fat globule membrane (MFGM) glycoproteins, MFG-E8, butyrophilin, CD36 was analyzed by Northern blot analyses...
  6. Chogle A, Bu H, Wang X, Brown J, Chou P, Tan X. Milk fat globule-EGF factor 8 is a critical protein for healing of dextran sodium sulfate-induced acute colitis in mice. Mol Med. 2011;17:502-7 pubmed publisher
    ..These data suggest that MGF-E8 is an essential protective factor for gut epithelial homeostasis, and exogenous administration of MFG-E8 may represent a novel therapeutic target in inflammatory bowel disease. ..
  7. Friggeri A, Yang Y, Banerjee S, Park Y, Liu G, Abraham E. HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin. Am J Physiol Cell Physiol. 2010;299:C1267-76 pubmed publisher
    ..These results demonstrate that HMGB1 blocks ?(v)?(3)-dependent recognition and uptake of apoptotic cells. ..
  8. Kranich J, Krautler N, Heinen E, Polymenidou M, Bridel C, Schildknecht A, et al. Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8. J Exp Med. 2008;205:1293-302 pubmed publisher
    The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis)...
  9. Yamaguchi H, Takagi J, Miyamae T, Yokota S, Fujimoto T, Nakamura S, et al. Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus. J Leukoc Biol. 2008;83:1300-7 pubmed publisher
    ..These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE. ..

More Information

Publications80

  1. Boddaert J, Kinugawa K, Lambert J, Boukhtouche F, Zoll J, Merval R, et al. Evidence of a role for lactadherin in Alzheimer's disease. Am J Pathol. 2007;170:921-9 pubmed
    b>Lactadherin is a secreted extracellular matrix protein expressed in phagocytes and contributes to the removal of apoptotic cells...
  2. Hanayama R, Nagata S. Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8. Proc Natl Acad Sci U S A. 2005;102:16886-91 pubmed
    ..These results demonstrate that MFG-E8-mediated phagocytosis of apoptotic epithelial cells and MFGs is important for efficient involution of mammary glands. ..
  3. Komura H, Miksa M, Wu R, Goyert S, Wang P. Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis via the lipopolysaccharide-CD14 pathway. J Immunol. 2009;182:581-7 pubmed
    ..Thus, MFG-E8 production is down-regulated in sepsis by LPS-CD14 dependent fashion, leading to a reduction of phagocytosis of apoptotic cells. ..
  4. Fricker M, Neher J, Zhao J, Théry C, Tolkovsky A, Brown G. MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation. J Neurosci. 2012;32:2657-66 pubmed publisher
    Milk-fat globule EGF factor-8 (MFG-E8, SED1, lactadherin) is known to mediate the phagocytic removal of apoptotic cells by bridging phosphatidylserine (PS)-exposing cells and the vitronectin receptor (VR) on phagocytes...
  5. Atabai K, Jame S, Azhar N, Kuo A, Lam M, McKleroy W, et al. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J Clin Invest. 2009;119:3713-22 pubmed publisher
    Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance...
  6. Jinushi M, Nakazaki Y, Dougan M, Carrasco D, Mihm M, Dranoff G. MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF. J Clin Invest. 2007;117:1902-13 pubmed
    ..These findings clarify the immunoregulatory effects of apoptotic cells and suggest new therapeutic strategies to modulate CD4(+) T cell subsets in cancer and autoimmunity. ..
  7. Aoki N, Kishi M, Taniguchi Y, Adachi T, Nakamura R, Matsuda T. Molecular cloning of glycoprotein antigens MGP57/53 recognized by monoclonal antibodies raised against bovine milk fat globule membrane. Biochim Biophys Acta. 1995;1245:385-91 pubmed
    ..and 53 kDa antigens (MGP57/53) recognized by monoclonal antibodies raised against bovine milk fat globule membrane (MFGM) (Biochim. Biophys...
  8. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature. 2002;417:182-7 pubmed
    ..These results indicate that MFG-E8 secreted from activated macrophages binds to apoptotic cells, and brings them to phagocytes for engulfment. ..
  9. Stubbs J, Lekutis C, Singer K, Bui A, Yuzuki D, Srinivasan U, et al. cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences. Proc Natl Acad Sci U S A. 1990;87:8417-21 pubmed
    ..mRNA expression was detectable in mammary tissue from nonpregnant animals but was maximal in the lactating gland. In cultured cells, mRNA levels also correlated with the degree of cellular differentiation. ..
  10. Miyanishi M, Segawa K, Nagata S. Synergistic effect of Tim4 and MFG-E8 null mutations on the development of autoimmunity. Int Immunol. 2012;24:551-9 pubmed publisher
    ..Milk Fat Globule EGF Factor VIII (MFG-E8) is secreted by one subset of macrophages, whereas Tim4, a type I membrane protein, is expressed by ..
  11. Asano K, Miwa M, Miwa K, Hanayama R, Nagase H, Nagata S, et al. Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice. J Exp Med. 2004;200:459-67 pubmed
    ..These results indicated that the impairment of apoptotic cell phagocytosis led to autoantibody production. ..
  12. Burgess B, Abrams T, Nagata S, Hall M. MFG-E8 in the retina and retinal pigment epithelium of rat and mouse. Mol Vis. 2006;12:1437-47 pubmed
    ..The localization of this glycoprotein in the retina and RPE, and particularly the specific localization of MFG-E8L in the RPE, suggests that this molecule may play an important, but as yet unknown role in retinal function. ..
  13. Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y, et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science. 2004;304:1147-50 pubmed
    ..These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases. ..
  14. Nandrot E, Anand M, Almeida D, Atabai K, Sheppard D, Finnemann S. Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis. Proc Natl Acad Sci U S A. 2007;104:12005-10 pubmed
    ..Thus, MFG-E8 stimulates rhythmic POS phagocytosis by ligating apical alphavbeta5 receptors of the RPE. These results identify MFG-E8 as the first extracellular ligand in the retina that is essential for diurnal POS phagocytosis. ..
  15. Sugano G, Bernard Pierrot I, Lae M, Battail C, Allory Y, Stransky N, et al. Milk fat globule--epidermal growth factor--factor VIII (MFGE8)/lactadherin promotes bladder tumor development. Oncogene. 2011;30:642-53 pubmed publisher
    Milk fat globule-epidermal growth factor-factor VIII (MFGE8), also called lactadherin or SED1, is a secreted integrin-binding protein that promotes elimination of apoptotic cells by phagocytes leading to tolerogenic immune responses, and ..
  16. Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka Akita H, et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci U S A. 2011;108:12425-30 pubmed publisher
    ..Thus, the pharmacological targeting of key factors derived from tumor-associated inflammation provides a unique strategy to eradicate therapy-resistant tumors by manipulating CSC activities. ..
  17. Bu H, Zuo X, Wang X, Ensslin M, Koti V, Hsueh W, et al. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007;117:3673-83 pubmed
    Milk fat globule-EGF factor 8 (MFG-E8)/lactadherin participates in several cell surface-mediated regulatory events...
  18. Brissette M, Lepage S, Lamonde A, Sirois I, Groleau J, Laurin L, et al. MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming. PLoS ONE. 2012;7:e36368 pubmed publisher
    ..Taken together, our study suggests a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming and demonstrates the importance of the apoptotic microenvironment in anti-inflammatory macrophage responses. ..
  19. Ensslin M, Shur B. The EGF repeat and discoidin domain protein, SED1/MFG-E8, is required for mammary gland branching morphogenesis. Proc Natl Acad Sci U S A. 2007;104:2715-20 pubmed
    b>SED1, also known as MFG-E8, is a secreted protein composed of two EGF repeats (the second of which contains an RGD motif) and two discoidin/Factor V/VIII C domains...
  20. Aziz M, Jacob A, Matsuda A, Wu R, Zhou M, Dong W, et al. Pre-treatment of recombinant mouse MFG-E8 downregulates LPS-induced TNF-? production in macrophages via STAT3-mediated SOCS3 activation. PLoS ONE. 2011;6:e27685 pubmed publisher
    ..Our findings strongly suggest that MFG-E8 is a direct anti-inflammatory molecule, and that it could be developed as a therapy in attenuating inflammation and tissue injury. ..
  21. Aziz M, Jacob A, Matsuda A, Wang P. Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation. Apoptosis. 2011;16:1077-86 pubmed publisher
    ..With the relevant cumulative findings, herein we reviewed the potential roles of MFG-E8 in pathophysiological conditions by highlighting its plausible signal-transduction mechanisms. ..
  22. Peng Y, Elkon K. Autoimmunity in MFG-E8-deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens. J Clin Invest. 2011;121:2221-41 pubmed publisher
    ..Older Mfge8-/- mice spontaneously developed dermatitis associated with CD8+ T cell infiltration and striking activation of ..
  23. Kranich J, Krautler N, Falsig J, Ballmer B, Li S, Hutter G, et al. Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain-dependent manner. J Exp Med. 2010;207:2271-81 pubmed publisher
    ..Engulfment of apoptotic bodies by phagocytes is mediated by Mfge8 (milk fat globule epidermal growth factor 8)...
  24. Oshima K, Aoki N, Negi M, Kishi M, Kitajima K, Matsuda T. Lactation-dependent expression of an mRNA splice variant with an exon for a multiply O-glycosylated domain of mouse milk fat globule glycoprotein MFG-E8. Biochem Biophys Res Commun. 1999;254:522-8 pubmed
  25. Cui T, Miksa M, Wu R, Komura H, Zhou M, Dong W, et al. Milk fat globule epidermal growth factor 8 attenuates acute lung injury in mice after intestinal ischemia and reperfusion. Am J Respir Crit Care Med. 2010;181:238-46 pubmed publisher
    ..MFG-E8 attenuates inflammation and ALI after gut I/R and may represent a novel therapeutic agent. ..
  26. Jinushi M, Sato M, Kanamoto A, Itoh A, Nagai S, Koyasu S, et al. Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms. J Exp Med. 2009;206:1317-26 pubmed publisher
    ..Collectively, these findings suggest that systemic MFG-E8 blockade might intensify the antitumor activities of existing therapeutic regimens through coordinated cell-autonomous and immune-mediated mechanisms. ..
  27. Hanayama R, Tanaka M, Miwa K, Nagata S. Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J Immunol. 2004;172:3876-82 pubmed
    ..These results suggest the existence of macrophage subsets that use MFG-E8 or Del-1 differently to engulf apoptotic cells. ..
  28. Silvestre J, Thery C, Hamard G, Boddaert J, Aguilar B, Delcayre A, et al. Lactadherin promotes VEGF-dependent neovascularization. Nat Med. 2005;11:499-506 pubmed
    ..We now show that an integrin-binding protein initially described in milk-fat globule, MFG-E8 (also known as lactadherin), is expressed in and around blood vessels and has a crucial role in VEGF-dependent neovascularization in the ..
  29. Aziz M, Ishihara S, Mishima Y, Oshima N, Moriyama I, Yuki T, et al. MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling. J Immunol. 2009;182:7222-32 pubmed publisher
    ..Taken together, our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis. ..
  30. Neher J, Emmrich J, Fricker M, Mander P, Thery C, Brown G. Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci U S A. 2013;110:E4098-107 pubmed publisher
    ..Therefore, inhibition of specific phagocytic pathways may present therapeutic targets for preventing delayed neuronal loss after transient cerebral ischemia. ..
  31. Naka M, Kusakabe K, Takeshita A, Nakagawa H, Ito Y, Shibata M, et al. Phagocytosis mechanism of apoptotic granulosa cells regulated by milk-fat globule-EGF factor 8. Med Mol Morphol. 2009;42:143-9 pubmed publisher
    ..MFG-E8 seems to act on the phagocytosis of apoptotic granulosa cells via macrophages and contribute to the regression process of atretic follicles. ..
  32. A Gonzalez N, Quintana J, Garcia Silva S, Mazariegos M, González de la Aleja A, Nicolás Ávila J, et al. Phagocytosis imprints heterogeneity in tissue-resident macrophages. J Exp Med. 2017;214:1281-1296 pubmed publisher
    ..Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis. ..
  33. Nakaya M, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, et al. GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance. Nat Commun. 2013;4:1532 pubmed publisher
    ..Our results reveal previously unrecognized roles for GRK6 in regulating apoptotic engulfment and its fundamental importance in immune and iron homoeostasis. ..
  34. Ye H, Li B, Subramanian V, Choi B, Liang Y, Harikishore A, et al. NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine. Biochim Biophys Acta. 2013;1828:1083-93 pubmed publisher
    MFG-E8 (also known as lactadherin), which is a secreted glycoprotein from a variety of cell types, possesses two EGF domains and tandem C domains with sequence homology to that of blood coagulation proteins factor V and factor VIII...
  35. Watanabe T, Totsuka R, Miyatani S, Kurata S, Sato S, Katoh I, et al. Production of the long and short forms of MFG-E8 by epidermal keratinocytes. Cell Tissue Res. 2005;321:185-93 pubmed
    Mouse milk fat globule-EGF factor 8, MFG-E8, is the ortholog to the human mammary tumor marker, lactadherin, and comprises two spliced variants, the L and S forms...
  36. Matsuda A, Jacob A, Wu R, Zhou M, Aziz M, Wang P. Milk fat globule--EGF factor VIII ameliorates liver injury after hepatic ischemia-reperfusion. J Surg Res. 2013;180:e37-46 pubmed publisher
    ..It has been previously shown that administration of milk fat globule-EGF factor VIII (MFG-E8), a membrane-associated secretory glycoprotein, exerts significant beneficial effects under acute ..
  37. Miksa M, Wu R, Dong W, Komura H, Amin D, Ji Y, et al. Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected]. J Immunol. 2009;183:5983-90 pubmed publisher
    ..Immature dendritic cells (IDCs) release exosomes that contain milk fat globule EGF factor VIII (MFGE8), a protein required to opsonize apoptotic cells for phagocytosis...
  38. Liu Y, Yang X, Guo C, Nie P, Liu Y, Ma J. Essential role of MFG-E8 for phagocytic properties of microglial cells. PLoS ONE. 2013;8:e55754 pubmed publisher
    ..Our results confirm that MFG-E8 plays an important role in phagocytosis, and possibly serves as an essential signal molecule for microglial cells. ..
  39. Soki F, Koh A, Jones J, Kim Y, Dai J, Keller E, et al. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J Biol Chem. 2014;289:24560-72 pubmed publisher
    ..These results uncover a unique role of efferocytosis via MFG-E8 as a mechanism for macrophage polarization into tumor-promoting M2 cells. ..
  40. Cheyuo C, Aziz M, Yang W, Jacob A, Zhou M, Wang P. Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem cell proliferation and migration after cerebral ischemia. PLoS ONE. 2015;10:e0122833 pubmed publisher
    ..Milk fat globule-EGF Factor VIII (MFG-E8), a secreted glycoprotein serves several cellular functions by binding to its receptor, αv β3-..
  41. Wang X, Bu H, Liu S, De Plaen I, Tan X. Molecular Mechanisms Underlying the Regulation of the MFG-E8 Gene Promoter Activity in Physiological and Inflammatory Conditions. J Cell Biochem. 2015;116:1867-79 pubmed publisher
    ..Collectively, our data indicate that Sp1 and AP-1-related factors are involved in the regulation of MFG-E8 gene transcription by targeting their binding sites in the 5'-flanking region under physiological and inflammatory states. ..
  42. Carrascosa C, Obula R, Missiaglia E, Lehr H, Delorenzi M, Frattini M, et al. MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells. Oncogene. 2012;31:1521-32 pubmed publisher
    ..We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development. ..
  43. Albus E, Sinningen K, Winzer M, Thiele S, Baschant U, Hannemann A, et al. Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) Is a Novel Anti-inflammatory Factor in Rheumatoid Arthritis in Mice and Humans. J Bone Miner Res. 2016;31:596-605 pubmed publisher
    ..Thus, MFG-E8 is a protective factor in the pathogenesis of RA and subsequent bone loss. Whether MFG-E8 qualifies as a novel biomarker or therapeutic target for the treatment of RA is worth addressing in further studies. ..
  44. Ensslin M, Vogel T, Calvete J, Thole H, Schmidtke J, Matsuda T, et al. Molecular cloning and characterization of P47, a novel boar sperm-associated zona pellucida-binding protein homologous to a family of mammalian secretory proteins. Biol Reprod. 1998;58:1057-64 pubmed
    b>P47, a peripherally associated 47-kDa protein of porcine spermatozoa, was identified by affinity chromatography in the fraction of solubilized plasma membrane proteins bound to immobilized porcine zona pellucida glycoproteins...
  45. Nakatani H, Aoki N, Nakagawa Y, Jin no S, Aoyama K, Oshima K, et al. Weaning-induced expression of a milk-fat globule protein, MFG-E8, in mouse mammary glands, as demonstrated by the analyses of its mRNA, protein and phosphatidylserine-binding activity. Biochem J. 2006;395:21-30 pubmed
    ..The weaning-induced MFG-E8 might play an important role in the recognition and engulfment of apoptotic epithelial cells by the neighbouring phagocytic epithelial cells in involuting mammary glands. ..
  46. Uchiyama A, Motegi S, Sekiguchi A, Fujiwara C, Perera B, Ogino S, et al. Mesenchymal stem cells-derived MFG-E8 accelerates diabetic cutaneous wound healing. J Dermatol Sci. 2017;86:187-197 pubmed publisher
    ..MSCs-derived MFG-E8 might accelerate diabetic wound healing by promoting angiogenesis, the clearance of apoptotic cells, and the infiltration of M2 macrophages, and by suppressing inflammatory cytokines in wound area. ..
  47. Uchiyama A, Yamada K, Perera B, Ogino S, Yokoyama Y, Takeuchi Y, et al. Protective effect of MFG-E8 after cutaneous ischemia-reperfusion injury. J Invest Dermatol. 2015;135:1157-1165 pubmed publisher
    ..Exogenous application of MFG-E8 might have therapeutic potential for cutaneous I/R injuries, including decubitus ulcers and Raynaud's phenomenon-induced digital ulcers. ..
  48. Ensslin M, Shur B. Identification of mouse sperm SED1, a bimotif EGF repeat and discoidin-domain protein involved in sperm-egg binding. Cell. 2003;114:405-17 pubmed
    We report the identification of SED1, a protein required for mouse sperm binding to the egg zona pellucida...
  49. Mishiro T, Kusunoki R, Otani A, Ansary M, Tongu M, Harashima N, et al. Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 8. Lab Invest. 2013;93:834-43 pubmed publisher
    ..Our novel findings suggest that butyric acid has significant anti-inflammatory effects partly via MFG-E8 on DSS-induced murine experimental colitis...
  50. Chaboub L, Manalo J, Lee H, Glasgow S, Chen F, Kawasaki Y, et al. Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during Development and after Injury. J Neurosci. 2016;36:11904-11917 pubmed
    ..These studies identify distinct stages of astrocyte lineage development and highlight the parallels between astrocyte development and their reactive counterparts associated with injury. ..
  51. Das A, Ghatak S, Sinha M, Chaffee S, Ahmed N, Parinandi N, et al. Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes. J Immunol. 2016;196:5089-100 pubmed publisher
    ..Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care. ..
  52. Khalifeh Soltani A, Ha A, Podolsky M, McCarthy D, McKleroy W, Azary S, et al. ?8?1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism. elife. 2016;5: pubmed publisher
    ..Mechanistically, ligation of ?8?1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism...
  53. Ooishi T, Nadano D, Matsuda T, Oshima K. Extracellular vesicle-mediated MFG-E8 localization in the extracellular matrix is required for its integrin-dependent function in mouse mammary epithelial cells. Genes Cells. 2017;22:885-899 pubmed publisher
    ..These results suggest that MFG-E8 requires EVs to transduce cellular signals from the basolateral side of the adhesion cells by accumulating in ECM. ..
  54. Zhang Z, Li B, Li X, Cheng M, Yu F, Lu W, et al. Proteomic analysis of kidney and protective effects of grape seed procyanidin B2 in db/db mice indicate MFG-E8 as a key molecule in the development of diabetic nephropathy. Biochim Biophys Acta. 2013;1832:805-16 pubmed publisher
  55. Chikazawa M, Otaki N, Shibata T, Yasueda T, Matsuda T, Uchida K. An apoptosis-associated mammary protein deficiency leads to enhanced production of IgM antibodies against multiple damage-associated molecules. PLoS ONE. 2013;8:e68468 pubmed publisher
  56. Raoul W, Poupel L, Tregouet D, Lavalette S, Camelo S, Keller N, et al. MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo. PLoS ONE. 2012;7:e33244 pubmed publisher
    Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization...
  57. Morelli A, Larregina A, Shufesky W, Sullivan M, Stolz D, Papworth G, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004;104:3257-66 pubmed
    ..Targeting of exosomes to DCs is mediated via milk fat globule (MFG)-E8/lactadherin, CD11a, CD54, phosphatidylserine, and the tetraspanins CD9 and CD81 on the exosome and alpha(v)/beta(3) ..
  58. Collins C, Nehlin J, Stubbs J, Kowbel D, Kuo W, Parry G. Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25. Genomics. 1997;39:117-8 pubmed
  59. Ait Oufella H, Kinugawa K, Zoll J, Simon T, Boddaert J, Heeneman S, et al. Lactadherin deficiency leads to apoptotic cell accumulation and accelerated atherosclerosis in mice. Circulation. 2007;115:2168-77 pubmed
    ..Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic ..
  60. Yoshino M, Yamazaki H, Hayashi S. Analysis of capturing skin antigens in the steady state using milk fat globule EGF factor 8-deficient skin-hyperpigmented mice. Immunol Lett. 2008;115:131-7 pubmed
    ..the accumulation of melanin granules (MGs), a marker of skin Ags, transported from the skin to regional LNs in Mfge8-deficient mice...
  61. Dasgupta S, Abdel Monem H, Niravath P, Le A, Bellera R, Langlois K, et al. Lactadherin and clearance of platelet-derived microvesicles. Blood. 2009;113:1332-9 pubmed publisher
    ..We tested the effect of lactadherin, which promotes the phagocytosis of phosphatidylserine-expressing lymphocytes and red blood cells, in the ..
  62. Spittau B, Rilka J, Steinfath E, Zöller T, Krieglstein K. TGF?1 increases microglia-mediated engulfment of apoptotic cells via upregulation of the milk fat globule-EGF factor 8. Glia. 2015;63:142-53 pubmed publisher
    Milk fat globule-epidermal growth factor-factor 8 (Mfge8) has been described as an essential molecule during microglia-mediated clearance of apoptotic cells via binding to phosphatidylserine residues and subsequent phagocytosis...
  63. Abe T, Shin J, Hosur K, Udey M, Chavakis T, Hajishengallis G. Regulation of osteoclast homeostasis and inflammatory bone loss by MFG-E8. J Immunol. 2014;193:1383-91 pubmed publisher
    ..Bone marrow-derived osteoclast precursors from MFG-E8-deficient (Mfge8(-/-)) mice underwent increased receptor activator of NF-?B ligand-induced osteoclastogenesis, leading to enhanced ..
  64. Deroide N, Li X, Lerouet D, Van Vré E, Baker L, Harrison J, et al. MFGE8 inhibits inflammasome-induced IL-1? production and limits postischemic cerebral injury. J Clin Invest. 2013;123:1176-81 pubmed publisher
    Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity...
  65. Baghdadi M, Chiba S, Yamashina T, Yoshiyama H, Jinushi M. MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals. PLoS ONE. 2012;7:e39607 pubmed publisher
    ..Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity. ..
  66. Lee J, Choi B, Park S, An S, Han J, Kim J. Fetal hematopoietic stem cells express MFG-E8 during mouse embryogenesis. Exp Mol Med. 2015;47:e174 pubmed publisher
    ..Together, this study demonstrates, for the first time, that MFG-8 is expressed in fetal HSC populations, and that MFG-E8 may have a role in embryonic hematopoiesis. ..
  67. Bocca S, Anderson S, Amaker B, Swanson R, Franchi A, Lattanzio F, et al. Milk fat globule epidermal growth factor 8 (MFG-E8): a novel protein in the mammalian endometrium with putative roles in implantation and placentation. Placenta. 2012;33:795-802 pubmed publisher
    ..MFG-E8 expression in the endometrial epithelium as well as in chorionic villi suggests its possible role in endometrial reorganization during the receptive phase and in events related to normal pregnancy in mammals. ..
  68. Nakatani H, Yasueda T, Oshima K, Okajima T, Nadano D, Flint D, et al. Post-weaning increases in the milk-fat globule EGF-factor VIII on fat globules in mouse milk and in the uptake of the fat globules by HC11 mammary epithelial cells. J Biochem. 2013;153:31-41 pubmed publisher
    ..We report here post-weaning changes in MFG EGF factor VIII (MFG-E8) and annexin V-accessible phosphatidyl-l-serine on the surface of MFGs...
  69. Kudo M, Khalifeh Soltani S, Sakuma S, McKleroy W, Lee T, Woodruff P, et al. Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction. Proc Natl Acad Sci U S A. 2013;110:660-5 pubmed publisher
    ..Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma...
  70. Yamada K, Uchiyama A, Uehara A, Perera B, Ogino S, Yokoyama Y, et al. MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages. Cancer Res. 2016;76:4283-92 pubmed publisher
    ..Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283-92. ©2016 AACR. ..
  71. Atabai K, Fernandez R, Huang X, Ueki I, Kline A, Li Y, et al. Mfge8 is critical for mammary gland remodeling during involution. Mol Biol Cell. 2005;16:5528-37 pubmed
    ..Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to ..