bone morphogenic protein-6

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BMP-6
BMP-6
BMP-6

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英文文献

  • The small molecule, genistein, increases hepcidin expression in human hepatocytes.
  • Zhen AW1, Nguyen NH, Gibert Y, Motola S, Buckett P, Wessling-Resnick M, Fraenkel E, Fraenkel PG.Author information 1Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.AbstractHepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP6) and interleukin-6 (IL-6) by effects on mothers against decapentaplegic homolog (Smad)4 or signal transducer and activator of transcription (Stat)3, respectively. We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression. We found that treatment with the isoflavone, genistein, from 28-52 hours postfertilization in zebrafish embryos enhanced Hepcidin transcript levels, as assessed by whole-mount in situ hybridization and quantitative real-time reverse-transcriptase polymerase chain reaction. Genistein's stimulatory effect was conserved in human hepatocytes: Genistein treatment of HepG2 cells increased both Hepcidin transcript levels and promoter activity. We found that genistein's effect on Hepcidin expression did not depend on estrogen receptor signaling or increased cellular iron uptake, but was impaired by mutation of either BMP response elements or the Stat3-binding site in the Hepcidin promoter. RNA sequencing of transcripts from genistein-treated hepatocytes indicated that genistein up-regulated 68% of the transcripts that were up-regulated by BMP6; however, genistein raised levels of several transcripts involved in Stat3 signaling that were not up-regulated by BMP6. Chromatin immunoprecipitation and ELISA experiments revealed that genistein enhanced Stat3 binding to the Hepcidin promoter and increased phosphorylation of Stat3 in HepG2 cells. Conclusion: Genistein is the first small-molecule experimental drug that stimulates Hepcidin expression in vivo and in vitro. These experiments demonstrate the feasibility of identifying and characterizing small molecules that increase Hepcidin expression. Genistein and other candidate molecules may subsequently be developed into new therapies for iron overload syndromes.
  • Hepatology (Baltimore, Md.).Hepatology.2013 Oct;58(4):1315-25. doi: 10.1002/hep.26490. Epub 2013 Aug 19.
  • Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morpho
  • PMID 23703590
  • Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling.
  • Besson-Fournier C1, Latour C, Kautz L, Bertrand J, Ganz T, Roth MP, Coppin H.Author information 1INSERM U1043, CHU Purpan, Toulouse Cedex 3, France.AbstractAnemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the inflammatory context is still not understood completely. In the present study, we show that activin B has an unexpected but crucial role in the induction of hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding the activin β(B)-subunit, in the livers of mice challenged with lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma-derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates hepcidin expression markedly, an observation confirmed in mouse primary hepatocytes. Pretreatment with a bone morphogenic protein type I receptor inhibitor showed that the effect of activin B on hepcidin expression is entirely attributable to its effect on bone morphogenetic protein signaling, most likely via activin receptor-like kinase 3. Activin B is therefore a novel and specific target for the treatment of anemia of inflammation.
  • Blood.Blood.2012 Jul 12;120(2):431-9. doi: 10.1182/blood-2012-02-411470. Epub 2012 May 18.
  • Anemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation i
  • PMID 22611157
  • Conditional inactivation of the CXCR4 receptor in osteoprecursors reduces postnatal bone formation due to impaired osteoblast development.
  • Zhu W1, Liang G, Huang Z, Doty SB, Boskey AL.Author information 1Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, New York 10021, USA. zhuw@hss.eduAbstractCysteine (C)-X-C motif chemokine receptor 4 (CXCR4), the primary receptor for stromal cell-derived factor-1 (SDF-1), is involved in bone morphogenic protein 2 (BMP2)-induced osteogenic differentiation of mesenchymal progenitors. To target the in vivo function of CXCR4 in bone and explore the underlying mechanisms, we conditionally inactivated CXCR4 in osteoprecursors by crossing osterix (Osx)-Cre mice with floxed CXCR4 (CXCR4(fl/fl)) mice to generate knock-outs with CXCR4 deletion driven by the Osx promoter (Osx::CXCR4(fl/fl)). The Cre-mediated excision of CXCR4 occurred exclusively in bone of Osx::CXCR4(fl/fl) mice. When compared with littermate controls, Osx::CXCR4(fl/fl) mice developed smaller osteopenic skeletons as evidenced by reduced trabecular and cortical bone mass, lower bone mineral density, and a slower mineral apposition rate. In addition, Osx::CXCR4(fl/fl) mice displayed chondrocyte disorganization in the epiphyseal growth plate associated with decreased proliferation and collagen matrix syntheses. Moreover, mature osteoblast-related expression of type I collagen α1 and osteocalcin was reduced in bone of Osx::CXCR4(fl/fl) mice versus controls, suggesting that CXCR4 deficiency results in arrested osteoblast progression. Primary cultures for osteoblastic cells derived from Osx::CXCR4(fl/fl) mice also showed decreased proliferation and impaired osteoblast differentiation in response to BMP2 or BMP6 stimulation, and suppressed activation of intracellular BMP receptor-regulated Smads (R-Smads) and Erk1/2 was identified in CXCR4-deficient cells and bone tissues. These findings provide the first in vivo evidence that CXCR4 functions in postnatal bone development by regulating osteoblast development in cooperation with BMP signaling. Thus, CXCR4 acts as an endogenous signaling component necessary for bone formation.
  • The Journal of biological chemistry.J Biol Chem.2011 Jul 29;286(30):26794-805. doi: 10.1074/jbc.M111.250985. Epub 2011 Jun 2.
  • Cysteine (C)-X-C motif chemokine receptor 4 (CXCR4), the primary receptor for stromal cell-derived factor-1 (SDF-1), is involved in bone morphogenic protein 2 (BMP2)-induced osteogenic differentiation of mesenchymal progenitors. To target the in vivo function of CXCR4 in bone and explore the underly
  • PMID 21636574

和文文献

  • 腸管細胞におけるBone Morphogenic Protein6の鉄による発現誘導はin vivoでの肝臓におけるヘプシジン発現の主要な調節因子である
  • 生田 克哉 [訳],高後 裕 [訳],Arndt Stephanie [他]
  • Review of gastroenterology & clinical gastroenterology and hepatology 5(2), 54-58, 2010-08
  • NAID 40017253404

関連リンク

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関連画像

Decrease in Expression of Bone FIGURE 1 | Bone morphogenetic protein (BMP You need to enable Javascript.FIGURE 2 | Formation of the neural tube by Description Protein BMP6 PDB 2QCW.pngBone morphogenetic protein signalling and


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関連記事bone」「protein」「boned」「bones」「morphogenic

bone」

  [★]

WordNet   license wordnet

「remove the bones from; "bone the turkey before roasting it"」
debone

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「the porous calcified substance from which bones are made」
osseous tissue

WordNet   license wordnet

「consisting of or made up of bone; "a bony substance"; "the bony framework of the body"」

WordNet   license wordnet

「a shade of white the color of bleached bones」
ivory, pearl, off-white

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「rigid connective tissue that makes up the skeleton of vertebrates」
os

PrepTutorEJDIC   license prepejdic

「〈C〉骨 / 〈U〉骨を作っている物質,骨質 / 《複数形で》骨格;死骸(がい) / 〈魚など〉‘の'骨を取る」

protein」

  [★] 蛋白質

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「any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"」

PrepTutorEJDIC   license prepejdic

「蛋白(たんばく)質」

boned」

  [★]

WordNet   license wordnet

「having bones as specified; "his lanky long-boned body"」

PrepTutorEJDIC   license prepejdic

「(魚など)骨を取り除いた / (衣服が)(コルセットなどで)骨で張りをつけた[ような]」

WordNet   license wordnet

「having had the bones removed; "a boneless rib roast"; "a boned (or deboned) fish"」
deboned


bones」

  [★]

WordNet   license wordnet

「a percussion instrument consisting of a pair of hollow pieces of wood or bone (usually held between the thumb and fingers) that are made to click together (as by Spanish dancers) in rhythm with the dance」
castanets, clappers, finger cymbals

morphogenic」

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  • 形態形成の
morphogenesismorphogenetic




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