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=Definition=
=Definition=
<span>Growth factors are a heterogeneous group of proteins which through specific binding of transmembrane receptors facilitate interactions between mesenchymal and epithelial cells and regulate many aspects of cellular function, such as survival, proliferation, migration and differentiation. Growth factors are essential for tissue development in the fetal period and for the maintenance of homeostasis in the adult body. The lack of growth factors increases apoptosis. Biologically active growth factors are produced by many types of cells residing in tissues, including mesenchymal stem cells. Depending on type and localization, they play a role in many biological processes, including determination of cell fate, mucosal morphogenesis and regeneration, epithelial turnover, establishing proper neuronal connectivity, or, in a pathological state, tumorigenesis.</span>
Growth factors are a heterogeneous group of proteins which through specific binding of transmembrane receptors facilitate interactions between mesenchymal and epithelial cells and regulate many aspects of cellular function, such as survival, proliferation, migration and differentiation. Growth factors are essential for tissue development in the fetal period and for the maintenance of homeostasis in the adult body. The lack of growth factors increases apoptosis. Biologically active growth factors are produced by many types of cells residing in tissues, including mesenchymal stem cells. Depending on type and localization, they play a role in many biological processes, including determination of cell fate, mucosal morphogenesis and regeneration, epithelial turnover, establishing proper neuronal connectivity, or, in a pathological state, tumorigenesis.
Growth factors and their receptors can be grouped into families based upon shared structural features, many of which are evolutionarily conserved; homologs of the fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) families can be found in a vast range of species, from nematodes or Drosophila to higher vertebrates.


<span>Czynniki wzrostu grupuje się w rodziny na podstawie wspólnych cech strukturalnych, z których wiele jest wysoce konserwatywne w toku ewolucji; homologi czynników wzrostu fibroblastów (FGF), naskórkowego czynnika wzrostu (EGF) czy transformującego czynnika wzrostu beta (TGF-β) znaleźć można u wielu gatunków, od nicieni i ''Drosophila'' po wyższe kręgowce.<span class="Apple-converted-space"></span></span>
=Examples of growth factors=
=Przykładowe czynniki wzrostu=
* '''FGF - ''' Fibroblast growth factors (FGF) are a large family of polypeptides acting as local or systemic cell signaling  molecules crucial for embryonic development, as well as tissue repair in the adult organism. Their structure and amino-acid sequence is highly conserved among vertebrates, and they are expressed in many, if not all tissues. They stimulate proliferation and inhibit apoptosis of cells derived from the mesoderm and neuroectoderm. These proteins play an important role in organogenesis, wound healing and angiogenesis. Apart from their function in cell proliferation, migration and differentiation, a subset of FGFs plays an important role in neuronal signal transduction. A characteristic property of FGFs is their high affinity for heparin; they require heparan sulfate to bind to one of the four types of their cell surface receptors. FGFs often signal across epithelial-mesenchymal boundaries stimulating cell proliferation and differentiation. Abnormal expression of FGFs is a factor in cancer pathogenesis  <ref>Ornitz DM, Marie PJ. Fibroblast growth factors in skeletal development. Curr Top Dev Biol. 2019;133:195-234. doi: 10.1016/bs.ctdb.2018.11.020 </ref> <ref>Mossahebi-Mohammadi M, Quan M, Zhang JS, Li X. FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency. Front Cell Dev Biol. 2020 Feb 18;8:79. doi: 10.3389/fcell.2020.00079 </ref>.
* '''EGF - ''' Epidermal growth factor (EGF) is a signalling protein found in multiple body fluids, e.g. milk, saliva, urine, blood plasma or amniotic fluid. EGF binds to the EGFR receptors, which in turn dimerize and induce tyrosine kinase activity. This initiates signalling cascades that affect various biological processes such as ion transportation, cell proliferation and differentiation, [[apoptoza/en|apoptosis]], embryonic development, organ development or tissue regeneration. Increased EGF/EGFR activity correlates with tumour growth and metastasis, particularly in glioblastomas, and lung, breast, colorectal, ovarian, prostate or pancreatic cancers  <ref>Zeng F, Harris RC. Epidermal growth factor, from gene organization to bedside. Semin Cell Dev Biol. 2014 Apr;28:2-11. doi: 10.1016/j.semcdb.2014.01.011 </ref> <ref>Romano R, Bucci C. Role of EGFR in the Nervous System. Cells. 2020 Aug 12;9(8):1887. doi: 10.3390/cells9081887 </ref>.
* '''TGF- β - ''' Transforming growth factor-β (TGFβ) is a signalling protein that plays a role in cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration via a serine/threonine kinase complex. There are three known isoforms of  TGFβ (TGFβ1, TGFβ2 and TGFβ3), and three types of TGFβ membrane receptors (TGF-β RI, TGF-β RII, TGF-β RIII). The transcriptional response to TGFβ in the cell is determined by the composition of the TGFβ signal transduction system (its ligands, receptors and regulators), its interaction with SMAD proteins, and the epigenetic modifications of target DNA. Most members of the TGFβ family act as paracrine factors on cells near the source <ref>Wang J, Xiang H, Lu Y, Wu T. Role and clinical significance of TGF‑β1 and TGF‑βR1 in malignant tumors (Review). Int J Mol Med. 2021 Apr;47(4):1. doi: 10.3892/ijmm.2021.4888 </ref> <ref>Martinez-Hackert E, Sundan A, Holien T. Receptor binding competition: A paradigm for regulating TGF-β family action. Cytokine Growth Factor Rev. 2021 Feb;57:39-54. doi: 10.1016/j.cytogfr.2020.09.003 </ref>.


* <span></span><span>'''FGF - '''Czynniki wzrostu fibroblastów (ang.fibroblast growth factors) to obszerna rodzina polipeptydów sygnałowych pełniących lokalne lub ogólnoustrojowe funkcje kluczowe w rozwoju zarodkowym oraz naprawie uszkodzonych tkanek w dorosłym organizmie. Ich struktura oraz sekwencja aminokwasów jest wysoce konserwatywna wśród kręgowców; można je również znaleźć w wielu, jeśli nie wszystkich rodzajach tkanek. Pobudzają proliferację i hamują apoptozę komórek wywodzących się z mezodermy i neuroektodermy. Białka te pełnią istotną rolę w<span class="Apple-converted-space"> </span>organogenezie, gojeniu ran oraz w angiogenezie. Oprócz pełnienia funkcji w proliferacji, migracji oraz różnicowaniu się komórek, specyficzne FGF odgrywają ważną rolę w szlakach sygnałowych układu nerwowego. Charakterystyczną cechą FGF jest ich wysokie powinowactwo z heparyną; wymagają one siarczanu heparanu, by związać się z jednym z czterech rodzajów receptorów powierzchniowych. FGF często generują powstawanie sygnałów poprzez barierę nabłonkowo-mezenchymalną pobudzając proliferację i różnicowanie się komórek. Nieprawidłowa ekspresja FGF jest czynnikiem prowadzącym do patogenezy związanej z rozwojem nowotworów.</span>
 
* <span></span><span>'''EGF - '''Naskórkowy czynnik wzrostu (ang. epidermal growth factor) to białko sygnałowe obecne w płynach ustrojowych, np. mleku, ślinie, moczu, osoczu krwi, czy płynie owodniowym. EGF wiąże się z receptorami EGFR (ang. epidermal growth factor receptor), powodując ich dimeryzację i aktywację kinazy tyrozynowej. Uruchomione w ten sposób kaskady sygnałowe wpływają na przebieg wielu procesów biologicznych, takich jak transport jonów, proliferacja i różnicowanie komórek, </span><span>[[apoptoza|apoptoza]]</span><span>, rozwój zarodkowy, rozwój narządów czy regeneracja tkanek. Nadmierna aktywność EGF i EGRF powiązana jest z rozwojem guzów nowotworowych oraz przerzutami nowotworów, w szczególności glejaków wielopostaciowych, nowotworów płuc, piersi, jelita grubego, jajnika, prostaty i trzustki.</span>
 
* <span>'''TGF- β - '''Transformujący czynnik wzrostu beta(ang. transforming growth factor-β) to białko sygnałowe odgrywające rolę w proliferacji i różnicowaniu komórek, morfogenezie, oraz homeostazie i regeneracji tkanek (w tym gojeniu ran). Znane są trzy izoformy TGF-β (TGF-β1,TGF-β2,TGF-β3), oraz trzy typy jego receptorów<span class="Apple-converted-space"> </span>błonowych (TGF-β RI, TGF-β RII, TGF-β RIII). Transkrypcyjna odpowiedź komórki na TGF-β jest uzależniona od kompozycji szlaku sygnałowego (poszczególnych ligandów, receptorów oraz regulatorów), interakcji TGF-β z białkami SMAD, oraz epigenetycznych modyfikacji docelowego fragmentu DNA. Większość białek z rodziny TGF-β działa parakrynnie – na komórki w pobliżu źródła ich wydzielania.</span><br  /><span></span>
=Bibliography=

Aktualna wersja na dzień 14:55, 10 mar 2021

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Definition

Growth factors are a heterogeneous group of proteins which through specific binding of transmembrane receptors facilitate interactions between mesenchymal and epithelial cells and regulate many aspects of cellular function, such as survival, proliferation, migration and differentiation. Growth factors are essential for tissue development in the fetal period and for the maintenance of homeostasis in the adult body. The lack of growth factors increases apoptosis. Biologically active growth factors are produced by many types of cells residing in tissues, including mesenchymal stem cells. Depending on type and localization, they play a role in many biological processes, including determination of cell fate, mucosal morphogenesis and regeneration, epithelial turnover, establishing proper neuronal connectivity, or, in a pathological state, tumorigenesis. Growth factors and their receptors can be grouped into families based upon shared structural features, many of which are evolutionarily conserved; homologs of the fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) families can be found in a vast range of species, from nematodes or Drosophila to higher vertebrates.

Examples of growth factors

  • FGF - Fibroblast growth factors (FGF) are a large family of polypeptides acting as local or systemic cell signaling  molecules crucial for embryonic development, as well as tissue repair in the adult organism. Their structure and amino-acid sequence is highly conserved among vertebrates, and they are expressed in many, if not all tissues. They stimulate proliferation and inhibit apoptosis of cells derived from the mesoderm and neuroectoderm. These proteins play an important role in organogenesis, wound healing and angiogenesis. Apart from their function in cell proliferation, migration and differentiation, a subset of FGFs plays an important role in neuronal signal transduction. A characteristic property of FGFs is their high affinity for heparin; they require heparan sulfate to bind to one of the four types of their cell surface receptors. FGFs often signal across epithelial-mesenchymal boundaries stimulating cell proliferation and differentiation. Abnormal expression of FGFs is a factor in cancer pathogenesis [1] [2].
  • EGF - Epidermal growth factor (EGF) is a signalling protein found in multiple body fluids, e.g. milk, saliva, urine, blood plasma or amniotic fluid. EGF binds to the EGFR receptors, which in turn dimerize and induce tyrosine kinase activity. This initiates signalling cascades that affect various biological processes such as ion transportation, cell proliferation and differentiation, apoptosis, embryonic development, organ development or tissue regeneration. Increased EGF/EGFR activity correlates with tumour growth and metastasis, particularly in glioblastomas, and lung, breast, colorectal, ovarian, prostate or pancreatic cancers [3] [4].
  • TGF- β - Transforming growth factor-β (TGFβ) is a signalling protein that plays a role in cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration via a serine/threonine kinase complex. There are three known isoforms of TGFβ (TGFβ1, TGFβ2 and TGFβ3), and three types of TGFβ membrane receptors (TGF-β RI, TGF-β RII, TGF-β RIII). The transcriptional response to TGFβ in the cell is determined by the composition of the TGFβ signal transduction system (its ligands, receptors and regulators), its interaction with SMAD proteins, and the epigenetic modifications of target DNA. Most members of the TGFβ family act as paracrine factors on cells near the source [5] [6].


Bibliography

  1. Ornitz DM, Marie PJ. Fibroblast growth factors in skeletal development. Curr Top Dev Biol. 2019;133:195-234. doi: 10.1016/bs.ctdb.2018.11.020
  2. Mossahebi-Mohammadi M, Quan M, Zhang JS, Li X. FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency. Front Cell Dev Biol. 2020 Feb 18;8:79. doi: 10.3389/fcell.2020.00079
  3. Zeng F, Harris RC. Epidermal growth factor, from gene organization to bedside. Semin Cell Dev Biol. 2014 Apr;28:2-11. doi: 10.1016/j.semcdb.2014.01.011
  4. Romano R, Bucci C. Role of EGFR in the Nervous System. Cells. 2020 Aug 12;9(8):1887. doi: 10.3390/cells9081887
  5. Wang J, Xiang H, Lu Y, Wu T. Role and clinical significance of TGF‑β1 and TGF‑βR1 in malignant tumors (Review). Int J Mol Med. 2021 Apr;47(4):1. doi: 10.3892/ijmm.2021.4888
  6. Martinez-Hackert E, Sundan A, Holien T. Receptor binding competition: A paradigm for regulating TGF-β family action. Cytokine Growth Factor Rev. 2021 Feb;57:39-54. doi: 10.1016/j.cytogfr.2020.09.003