Diferenzas entre revisións de «Factor de crecemento de hepatocitos»

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O '''factor de crecemento de hepatocitos''' ('''HGF''') (ou '''factor de dispersión''', en inglés ''scatter factor'' ou '''SF''') é un [[factor de crecemento]] celular [[parácrino]], de [[motilidade]] e [[morfóxeno|morfoxénico]]. É segregado polas células [[mesénquima|mesenquimais]] e ten como diana e actúa principalmente sobre [[célula epitelial|células epiteliais]] e [[célula endotelial|endoteliais]], pero tamén actúa sobre as [[haematopoese|células proxenitoras hematopoéticas]] e [[célula T|células T]]. Ten un importante papel no desenvolvemento de órganos embrionarios, especificamente na [[mioxénese]], na rexeneración de órganos adultos e na curación de feridas.<ref>{{citeCita booklibro | title=Proteoglycans: structure, biology and molecular interactions | author=Gallagher, J.T., Lyon, M. | chapter=Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens | editor=Iozzo, M, V. | year=2000 | publisher=Marcel Dekker Inc. New York, New York | pages=27–59}}</ref>
 
== Función ==
 
O factor de crecemento do hepatocito regula o crecemento celular, a motilidade celular e a [[morfoxénese]] ao activar a fervenza de sinalización da [[tirosina quinase]] despois de unirse ao receptor protooncoxénico [[c-Met]].<ref name="pmid1846706">{{citeCita journalpublicación periódica | vauthors = Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA | title = Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product | journal = Science | volume = 251 | issue = 4995 | pages = 802–4 | date = February 1991 | pmid = 1846706 | doi = 10.1126/science.1846706 }}</ref><ref>{{citeCita journalpublicación periódica | vauthors = Johnson M, Koukoulis G, Matsumoto K, Nakamura T, Iyer A | title = Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells | journal = Hepatology | volume = 17 | issue = 6 | pages = 1052–61 | date = June 1993 | pmid = 8514254 | doi = 10.1016/0270-9139(93)90122-4 }}</ref> O HGR é segregado polas [[célula nai mesenquimal|células mesenquimais]] e actúa como unha [[citocina]] multifuncional en células de orixe principalmente epitelial. A súa capacidade de estimular a [[mitoxénese]], motilidade celular e invasión da [[matriz extracelular|matriz]] dálle un papel central na [[anxioxénese]], [[tumoroxénese]] e rexeneración de tecidos.<ref name = "entrez" />
 
== Estrutura ==
 
Segrégase en forma dun só polipéptido inactivo e despois é clivado por [[serina protease]]s dando unha cadea alfa de 69 kDa e outra beta de 34 kDa. Unha [[ponte disulfuro]] entre as cadeas alfa e beta úneas dando lugar ao produto activo heterodimérico. A proteína pertence á subfamilia do [[plasminóxeno]] de [[peptidase]]s S1, pero non ten actividade detectable de [[protease]].<ref name = "entrez" >{{citeCita web | title = Entrez Gene: HGF hepatocyte growth factor (hepapoietin A; scatter factor)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3082| accessdate = }}</ref>
 
== Importancia clínica ==
 
A [[terapia de ADN de plásmido de HGF humano]] de [[cardiomiocito]]s está sendo examinada como posible tratamento da [[enfermidade da arteria coronaria]] e como traramento para os danos ocorridos no corazón despois dun [[infarto de miocardio]].<ref name=YangZhang2008>{{citeCita journalpublicación periódica | vauthors = Yang ZJ, Zhang YR, Chen B, Zhang SL, Jia EZ, Wang LS, Zhu TB, Li CJ, Wang H, Huang J, Cao KJ, Ma WZ, Wu B, Wang LS, Wu CT | title = Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease | journal = Molecular Biology Reports | volume = 36 | issue = 6 | pages = 1323–9 | date = July 2009 | pmid = 18649012 | pmc = | doi = 10.1007/s11033-008-9315-3 }}</ref><ref name=HahnPyun2011>{{citeCita journalpublicación periódica | vauthors = Hahn W, Pyun WB, Kim DS, Yoo WS, Lee SD, Won JH, Shin GJ, Kim JM, Kim S | title = Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model | journal = The Journal of Gene Medicine | volume = 13 | issue = 10 | pages = 549–55 | date = October 2011 | pmid = 21898720 | pmc = | doi = 10.1002/jgm.1603 }}</ref>
Ademais dos efectos ben caracterizados do HGF sobre as células epitaliais, endoteliais e proxenitoras hematopoéticas, o HGF tamén regula a [[quimiotaxe]] de [[célula T|células T]] no tecido cardíaco. A unión do HGF o c-Met, expresado en células T, causa a regulación á alza de c-Met, [[CXCR3]] e [[CCR4]], que á súa vez lles dá a capacidade de migrar ao tecido cardíaco.<ref name="pmid26070483">{{citeCita journalpublicación periódica | vauthors = Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, Cooper D, Nadkarni S, Fu H, Steinbruchel DA, Pitzalis C, Anderson G, Bucy P, Lombardi G, Breckenridge R, Marelli-Berg FM | title = Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release | journal = Immunity | volume = 42 | issue = 6 | pages = 1087–99 | date = September 2016 | pmid = 26070483 | pmc = 4510150 | doi = 10.1016/j.immuni.2015.05.014 }}</ref> O HGF tamén promociona a anxioxénese nas lesións isquémicas. <ref>{{citeCita journalpublicación periódica | vauthors = Chang HK, Kim PH, Cho, HM, Yum, SY, Choi, YJ, Lee D, Kang I, Kang KS, Jang G, Cho JY| title = Inducible HGF-secreting Human Umbilical Cord Blood-derived MSCs Produced via TALEN-mediated Genome Editing Promoted Angiogenesis | journal = Molecular Therapy | volume = 24 | issue = 9 | pages = 1644-54 | date = Sep 2016 | pmid = 27434585 | pmc = 5113099 | doi = 10.1038/mt.2016.120 }}</ref>
O HGF pode xogar un papel como indicador de prognóstico para a [[artralxia]] inducida polo [[virus]] [[Chikungunya]]. Os niveis altos de HGF correlaciónanse con altas taxas de recuperación.<ref name="pmid21288813">{{citeCita journalpublicación periódica | vauthors = Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, Kwek DJ, Barkham T, Yang H, Rénia L, Leo YS, Ng LF | title = Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor | journal = The Journal of Infectious Diseases | volume = 203 | issue = 2 | pages = 149–57 | date = January 2011 | pmid = 21288813 | pmc = 3071069 | doi = 10.1093/infdis/jiq042 }}</ref>
 
A expresión excesiva local de HGF nas [[glándula mamaria|mamas]] foi implicada na [[macromastia]].<ref name="ZhongWang2014">{{citeCita journalpublicación periódica | vauthors = Zhong A, Wang G, Yang J, Xu Q, Yuan Q, Yang Y, Xia Y, Guo K, Horch RE, Sun J | title = Stromal-epithelial cell interactions and alteration of branching morphogenesis in macromastic mammary glands | journal = Journal of Cellular and Molecular Medicine | volume = 18 | issue = 7 | pages = 1257–66 | date = July 2014 | pmid = 24720804 | doi = 10.1111/jcmm.12275 | pmc=4124011}}</ref> O HGFestá tamén implicado de forma importante no desenvolvemento normal da [[glándula mamaria]].<ref name="pmid7555716">{{citeCita journalpublicación periódica | vauthors = Niranjan B, Buluwela L, Yant J, Perusinghe N, Atherton A, Phippard D, Dale T, Gusterson B, Kamalati T | title = HGF/SF: a potent cytokine for mammary growth, morphogenesis and development | journal = Development | volume = 121 | issue = 9 | pages = 2897–908 | year = 1995 | pmid = 7555716 | doi = | url = }}</ref><ref name="pmid10219907">{{citeCita journalpublicación periódica | vauthors = Kamalati T, Niranjan B, Yant J, Buluwela L | title = HGF/SF in mammary epithelial growth and morphogenesis: in vitro and in vivo models | journal = J Mammary Gland Biol Neoplasia | volume = 4 | issue = 1 | pages = 69–77 | year = 1999 | pmid = 10219907 | doi = | url = }}</ref>
 
O HGF foi implicado en diversos [[cancro]]s, como o de [[pulmón]], [[páncreas]], [[tiroide]], [[colon]] e [[cancro de mama|mama]].<ref name="ZieglerPierce2012">{{citeCita booklibro|author1=Thomas R. Ziegler|author2=Glenn F. Pierce|author3=David N. Herndon|title=Growth Factors and Wound Healing: Basic Science and Potential Clinical Applications|url=https://books.google.com/books?id=5ct9BwAAQBAJ&pg=PA311|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-1876-0|pages=311–}}</ref><ref name="pmid15767355">{{citeCita journalpublicación periódica | vauthors = Sheen-Chen SM, Liu YW, Eng HL, Chou FF | title = Serum levels of hepatocyte growth factor in patients with breast cancer | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 14 | issue = 3 | pages = 715–7 | date = March 2005 | pmid = 15767355 | doi = 10.1158/1055-9965.EPI-04-0340 }}</ref><ref name="pmid21934211">{{citeCita journalpublicación periódica | vauthors = El-Attar HA, Sheta MI | title = Hepatocyte growth factor profile with breast cancer | journal = Indian Journal of Pathology & Microbiology | volume = 54 | issue = 3 | pages = 509–13 | year = 2011 | pmid = 21934211 | doi = 10.4103/0377-4929.85083 }}</ref>
 
O incremento da expresión de HGF foi asociada coas capacidades de mellora e non formación de cicatriz na [[curación de feridas]] de [[fibroblasto]]s illados do tecido da [[mucosa oral]].<ref>{{citeCita journalpublicación periódica | vauthors = Dally J, Khan JS, Voisey A, Charalambous C, John HL, Woods EL, Steadman R, Moseley R, Midgley AC | title = Hepatocyte Growth Factor Mediates Enhanced Wound Healing Responses and Resistance to Transforming Growth Factor-β₁-Driven Myofibroblast Differentiation in Oral Mucosal Fibroblasts | journal = International Journal of Molecular Sciences | volume = 18 | issue = 9 | date = August 2017 | pmid = 28837064 | pmc = 5618492 | doi = 10.3390/ijms18091843 }}</ref>
 
=== Niveis de plasma circulantes ===
O [[plasma sanguíneo|plasma]] de pacientes con insuficiencia cardíaca avanzada presenta niveis incrementados de HGF, o cal se correlaciona cun prognóstico negativo e un alto risco de mortalidade.<ref>{{citeCita journalpublicación periódica | vauthors = Richter B, Koller L, Hohensinner PJ, Zorn G, Brekalo M, Berger R, Mörtl D, Maurer G, Pacher R, Huber K, Wojta J, Hülsmann M, Niessner A | title = A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure | journal = International Journal of Cardiology | volume = 168 | issue = 2 | pages = 1251–7 | date = September 2013 | pmid = 23218577 | doi = 10.1016/j.ijcard.2012.11.052 }}</ref><ref>{{citeCita journalpublicación periódica | vauthors = Rychli K, Richter B, Hohensinner PJ, Kariem Mahdy A, Neuhold S, Zorn G, Berger R, Mörtl D, Huber K, Pacher R, Wojta J, Niessner A, Hülsmann M | title = Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure | journal = Heart | volume = 97 | issue = 14 | pages = 1158–63 | date = July 2011 | pmid = 21572126 | doi = 10.1136/hrt.2010.220228 }}</ref> O HGF circulante foi tamén identificado como marcador de prognóstico que indica gravidade en pacientes que padecen [[hipertensión arterial|hipertensión]].<ref name="ReferenceB">{{citeCita journalpublicación periódica | vauthors = Nakamura S, Morishita R, Moriguchi A, Yo Y, Nakamura Y, Hayashi S, Matsumoto K, Matsumoto K, Nakamura T, Higaki J, Ogihara T | title = Hepatocyte growth factor as a potential index of complication in diabetes mellitus | journal = Journal of Hypertension | volume = 16 | issue = 12 Pt 2 | pages = 2019–26 | date = December 1998 | pmid = 9886892 | doi = 10.1291/hypres.22.161 }}</ref><ref name="ReferenceB"/> O HGF circulante tamén se suxeriu como posible [[biomarcador]] precoz da fase aguda da [[inflamación]] intestinal.<ref>{{citeCita journalpublicación periódica | vauthors = Sorour AE, Lönn J, Nakka SS, Nayeri T, Nayeri F | title = Evaluation of hepatocyte growth factor as a local acute phase response marker in the bowel: the clinical impact of a rapid diagnostic test for immediate identification of acute bowel inflammation | journal = Cytokine | volume = 71 | issue = 1 | pages = 8–15 | date = January 2015 | pmid = 25174881 | doi = 10.1016/j.cyto.2014.07.255 }}</ref>
 
== Farmacocinética ==
O HGF exóxeno administrado por [[inxección intravenosa]] é eliminado rapidamente da circulación polo [[fígado]], e ten unha [[vida media]] de aproximadamente 4 minutos.<ref name="Yang2001">{{citeCita journalpublicación periódica | vauthors = Yang J, Chen S, Huang L, Michalopoulos GK, Liu Y | title = Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth | journal = Hepatology | volume = 33 | issue = 4 | pages = 848–59 | date = April 2001 | pmid = 11283849 | pmc = 1821076 | doi = 10.1053/jhep.2001.23438 }}</ref><ref name="pmid8450646">{{citeCita journalpublicación periódica | vauthors = Appasamy R, Tanabe M, Murase N, Zarnegar R, Venkataramanan R, Van Thiel DH, Michalopoulos GK | title = Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 68 | issue = 3 | pages = 270–6 | date = March 1993 | pmid = 8450646 | doi = }}</ref><ref name="KatoLiu1994">{{citeCita journalpublicación periódica | vauthors = Kato Y, Liu KX, Nakamura T, Sugiyama Y | title = Heparin-hepatocyte growth factor complex with low plasma clearance and retained hepatocyte proliferating activity | journal = Hepatology | volume = 20 | issue = 2 | pages = 417–24 | date = August 1994 | pmid = 8045504 | doi = 10.1002/hep.1840200223 }}</ref><ref name="YuYao2007">{{citeCita journalpublicación periódica | vauthors = Yu Y, Yao AH, Chen N, Pu LY, Fan Y, Lv L, Sun BC, Li GQ, Wang XH | title = Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration | journal = Molecular Therapy | volume = 15 | issue = 7 | pages = 1382–9 | date = July 2007 | pmid = 17519892 | doi = 10.1038/sj.mt.6300202 }}</ref>
 
== Moduladores ==
[[Dihexa]] é unha [[pequena molécula]] oralmente activa e penetrante centralmente que se une directamente ao HGF e potencia a súa capacidade de activar o seu receptor, c-Met.<ref name="BenoistKawas2014">{{citeCita journalpublicación periódica | vauthors = Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW | title = The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 351 | issue = 2 | pages = 390–402 | date = November 2014 | pmid = 25187433 | pmc = 4201273 | doi = 10.1124/jpet.114.218735 }}</ref> É un forte indutor da [[neuroxénese]] e está sendo estudada para a súa posible aplicación no tratamento da [[enfermidade de Alzheimer]] e a de [[enfermidade de Parkinson|Parkinson]].<ref name="pmid25649658">{{citeCita journalpublicación periódica | vauthors = Wright JW, Harding JW | title = The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease | journal = Journal of Alzheimer's Disease | volume = 45 | issue = 4 | pages = 985–1000 | year = 2015 | pmid = 25649658 | doi = 10.3233/JAD-142814 }}</ref><ref name="WrightKawas2015">{{citeCita journalpublicación periódica | vauthors = Wright JW, Kawas LH, Harding JW | title = The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases | journal = Progress in Neurobiology | volume = 125 | pages = 26–46 | date = February 2015 | pmid = 25455861 | doi = 10.1016/j.pneurobio.2014.11.004 }}</ref>
 
== Interaccións ==
O factor de crecemento de hepatocitos presenta [[interaccións proteína-proteína|interaccións]] co produto proteico do oncoxene c-Met, identificado como receptor de HGF ([[c-Met|HGFR]]).<ref name="pmid1846706"/><ref name="pmid8380735">{{citeCita journalpublicación periódica | vauthors = Comoglio PM | title = Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells | journal = Exs | volume = 65 | issue = | pages = 131–65 | year = 1993 | pmid = 8380735 | doi = }}</ref><ref name="pmid1655405">{{citeCita journalpublicación periódica | vauthors = Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan RP, Hartmann G, Zarnegar R, Michalopoulos GK | title = Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor | journal = The EMBO Journal | volume = 10 | issue = 10 | pages = 2867–78 | date = October 1991 | pmid = 1655405 | pmc = 452997 | doi = }}</ref> Tanto a sobreexpresión da proteína do receptor Met/HGFR coma a activación [[sinalización autócrina|autócrina]] de Met/HGFR pola expresión simultánea do [[ligando]] factor de crecemento de hepatocitos foron implicadas na [[oncoxénese]].<ref>{{citeCita journalpublicación periódica | vauthors = Johnson M, Koukoulis G, Kochhar K, Kubo C, Nakamura T, Iyer A | title = Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection | journal = Cancer Letters | volume = 96 | issue = 1 | pages = 37–48 | date = September 1995 | pmid = 7553606 | doi = 10.1016/0304-3835(95)03915-j }}</ref><ref>{{citeCita journalpublicación periódica | vauthors = Kochhar KS, Johnson ME, Volpert O, Iyer AP | title = Evidence for autocrine basis of transformation in NIH-3T3 cells transfected with met/HGF receptor gene | journal = Growth Factors | volume = 12 | issue = 4 | pages = 303–13 | date = 1995 | pmid = 8930021 | doi = 10.3109/08977199509028968 }}</ref>
O factor de crecemento de hepatocitos interacciona cos [[glicosaminoglicano]]s sufatados [[heparán sulfato]] e [[dermatán sulfato]].<ref name="ReferenceA">{{citeCita journalpublicación periódica | vauthors = Lyon M, Deakin JA, Gallagher JT | title = The mode of action of heparan and dermatan sulfates in the regulation of hepatocyte growth factor/scatter factor | journal = The Journal of Biological Chemistry | volume = 277 | issue = 2 | pages = 1040–6 | date = January 2002 | pmid = 11689562 | doi = 10.1074/jbc.M107506200 }}</ref><ref>{{citeCita journalpublicación periódica | vauthors = Lyon M, Deakin JA, Rahmoune H, Fernig DG, Nakamura T, Gallagher JT | title = Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate | journal = J Biol Chem | volume = 273 | issue = 1 | pages = 271–8. | date = Jan 1998 | PMID = 9417075 | doi = 10.1074/jbc.273.1.271 | url = http://www.jbc.org/content/273/1/271.long}}</ref> A interacción co heparán sulfato permite que o factor de crecemento de hepatocitos forme un complexo con c-Met que pode [[transdución de sinais|transducir sinais]] intracelulares que orixinarán a [[división celular]] e a [[migración celular]].<ref name="ReferenceA"/><ref>{{citeCita journalpublicación periódica | vauthors = Sergeant N, Lyon M, Rudland PS, Fernig DG, Delehedde M | title = Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 22 | pages = 17094–9 | date = June 2000 | pmid = 10747885 | doi = 10.1074/jbc.M000237200 }}</ref>
 
== Notas ==
 
=== Bibliografía ===
* {{citeCita journalpublicación periódica |vauthors=Michalopoulos GK, Zarnegar R |title=Hepatocyte Growth Factor |journal=Hepatology |volume=15 |issue=1 |pages= 149–54 |year= 1992 |doi=10.1002/hep.1840150125 }}
* {{citeCita journalpublicación periódica | vauthors = Nakamura T | title = Structure and function of hepatocyte growth factor | journal = Progress in Growth Factor Research | volume = 3 | issue = 1 | pages = 67–85 | year = 1992 | pmid = 1838014 | doi = 10.1016/0955-2235(91)90014-U }}
* {{citeCita journalpublicación periódica | vauthors = Ware LB, Matthay MA | title = Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair | journal = American Journal of Physiology. Lung Cellular and Molecular Physiology | volume = 282 | issue = 5 | pages = L924-40 | date = May 2002 | pmid = 11943656 | doi = 10.1152/ajplung.00439.2001 }}
* {{citeCita journalpublicación periódica | vauthors = Funakoshi H, Nakamura T | title = Hepatocyte growth factor: from diagnosis to clinical applications | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 327 | issue = 1–2 | pages = 1–23 | date = January 2003 | pmid = 12482615 | doi = 10.1016/S0009-8981(02)00302-9 }}
* {{citeCita journalpublicación periódica | vauthors = Skibinski G | title = The role of hepatocyte growth factor/c-met interactions in the immune system | journal = Archivum Immunologiae Et Therapiae Experimentalis | volume = 51 | issue = 5 | pages = 277–82 | year = 2004 | pmid = 14626426 | doi = }}
* {{citeCita journalpublicación periódica | vauthors = Kalluri R, Neilson EG | title = Epithelial-mesenchymal transition and its implications for fibrosis | journal = The Journal of Clinical Investigation | volume = 112 | issue = 12 | pages = 1776–84 | date = December 2003 | pmid = 14679171 | pmc = 297008 | doi = 10.1172/JCI20530 }}
* {{citeCita journalpublicación periódica | vauthors = Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG | title = Hepatocyte growth factor/scatter factor and prostate cancer: a review | journal = Histology and Histopathology | volume = 20 | issue = 4 | pages = 1339–49 | date = October 2005 | pmid = 16136515 | doi = 10.14670/HH-20.1339 }}
* {{citeCita journalpublicación periódica | vauthors = Kemp LE, Mulloy B, Gherardi E | title = Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 3 | pages = 414–7 | date = June 2006 | pmid = 16709175 | doi = 10.1042/BST0340414 }}
 
=== Ligazóns externas ===
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edicións