View More View Less
  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar, Budapest, Kútvölgyi út 4., 1125

Absztrakt:

Az írás a kis leucingazdag proteoglikánok összefoglalása után, amelyben utal a lurnican és a fibromodulin sajátosságaira, az inter-α-tripszin-inhibitorral foglalkozik. Kiderült, hogy a molekula eredetileg is tartalmaz savanyú glikánláncot a neutrális oligoszacharidok mellett. A proteoglikán gazdag kapcsolatrendszerének összefoglalása után kiemeli ezen szerkezet „önfeláldozó” funkcionális viselkedését. Ismeretes „akutfázis-reaktáns” volta mellett érinti az ovárium működését irányító szerepét, és említi antiinflammatorikus tulajdonságát. Ezt követően, a CD44-transzmembrán-szerkezet érintése után, összefoglalja sajátos hialuronánkapcsolatát, további élettani funkcióit és proteoglikán szerveződését. Ezután a hialuronán felépítésbeli sajátosságai, a fehérjementes láncstruktúrák kialakulása, a fragmentumok szerepe kerül tárgyalásra. A tanulmány összefoglalja az inter-α-tripszin-inhibitorral összefüggő, szerteágazó kapcsolódási rendszerben elfoglalt szerepet is. Röviden érintődnek a hialuronán élettani, kórélettani vonatkozásai. Megfogalmazódik a kötőszöveti alapállomány felépítésében, működésében, élettani és kóros viszonyok között betöltött nélkülözhetetlen szerep. Ezután érintődik a főbb, patológiás folyamatokat befolyásoló tevékenység, néhány klinikai vonatkozás. Röviden elmondható, hogy a hialuronsav egyedi fiziopatológiás szerepe az extracelluláris mátrix létrejöttében, működésében rejlik. Összefoglalva elmondható, hogy az inflammatiós folyamatok során a nagy, egész molekula antiinflammatiós, a rövidebb láncok, fragmentumok sokasága proinflammatiós szignalizációs hatást gyakorol. Az inter-α-tripszin-inhibitor struktúraszerveződést irányító molekula „beolvad” az egymással összefüggő, egymást feltételező processzusok sűrűjébe – bár tulajdonképpen eltűnik, hatásában azért tetten érhető. A TSG-6-ban és a C-reaktív fehérjében valódi, pozitív „akutfázis-reaktáns”-ra találhatunk. Orv Hetil. 2018; 159(16): 620–627.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1

    Fries E, Kaczmarczyk A. Inter-alpha-inhibitor, hyaluronan and inflammation. Acta Biochim Pol. 2003; 50: 735–742.

  • 2

    Garantziotis S, Hollingsworth JW, Ghanayem RB, et al. Inter-α-trypsin inhibitor attenuates complement activation and complement-induced lung injury. J Immunol. 2007; 179: 4187–4192.

  • 3

    Jakab L. The way of self-defence of the organism: inflammation. [A szervezeti önvédelem módja: a gyulladás.] Orv Hetil. 2013; 154: 1247–1255. [Hungarian]

  • 4

    Ceciliani F, Pocacqua V. The acute phase protein α1-acid glycoprotein: a model for altered glycosylation during diseases. Curr Protein Pept Sci. 2007; 8: 91–108.

  • 5

    Langford-Smith A, Day AJ, Bishop PN, et al. Complementing the sugar code: role of GAGs and sialic acid in complement regulation. Front Immunol. 2015; 6: 25.

  • 6

    Sjöberg P, Manderson GA, Mörgelin M, et al. Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation. Mol Immunol. 2009; 46: 830–839.

  • 7

    Johnson JM, Young TL, Rada JA. Small leucine rich repeat proteoglycans (SLRPs) in the human sclera: identification of abundant levels of PRELP. Mol Vis. 2006; 12: 1057–1066.

  • 8

    McEwan PA, Scott PG, Bishop PN, et al. Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans. J Struct Biol. 2006, 155: 294–305.

  • 9

    Matsushima N, Ohyanagi T, Tanaka T, et al. Super-motifs and evolution of tandem leucine-rich repeats within the small proteoglycans – biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, osteoadherin, epiphycan, and osteoglycin. Proteins 2000; 38: 210–225.

  • 10

    Groeneveld TW, Oroszlán M, Owens RT, et al. Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins. J Immunol. 2005; 175: 4715–4723.

  • 11

    Poon IK, Hulett MD, Parish CR. Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ. 2010; 17: 381–397.

  • 12

    Dube DH, Bertozzi CR. Glycans in cancer and inflammation – potential for therapeutics and diagnostics. Nat Rev Drug Discov. 2005; 4: 477–488.

  • 13

    Seidler DG. The galactosaminoglycan-containing decorin and its impact on diseases. Curr Opin Struct Biol. 2012; 22: 578–582.

  • 14

    Yamanaka O, Yuan Y, Coulson-Thomas VJ, et al. Lumican binds ALK5 to promote epithelium wound healing. PLoS ONE 2013; 8: e82730.

  • 15

    Jones AL, Hulett MD, Parish CR. Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems. Immunol Cell Biol. 2005; 83: 106–118.

  • 16

    Kalamajski S, Oldberg A. The role of small leucine-rich proteoglycans in collagen fibrillogenesis. Matrix Biol. 2010; 29: 248–253.

  • 17

    Wells JM, Gaggar A, Blalock JE. MMP generated matrikines. Matrix Biol. 2015; 44–46: 122–129.

  • 18

    López-Casillas F, Payne HM, Andres JL, et al. Betaglycan can act as a dual modulator of TGF-β access to signaling receptors: mapping of ligand binding and GAG attachment sites. J Cell Biol. 1994; 124: 557–568.

  • 19

    Rodriguez A, Friman T, Kowanetz M, et al. Phenotypical differences in connective tissue cells emerging from microvascular pericytes in response to overexpression of PDGF-B and TGF-β1 in normal skin in vivo. Am J Pathol. 2013; 182: 2132–2146.

  • 20

    Bost F, Diarra-Mehrpour M, Martin JP. Inter-α-trypsin inhibitor proteoglycan family – a group of proteins binding and stabilizing the extracellular matrix. Eur J Biochem. 1998; 252: 339–346.

  • 21

    Ly M, Leach FE, Laremore TN, et al. The proteoglycan bikunin has a defined sequence. Nat Chem Biol. 2011; 7: 827–833.

  • 22

    Gomez-Toledo A, Nilsson J, Noborn F, et al. Positive mode LC-MS/MS analysis of chondroitin sulfate modified glycopeptides derived from light and heavy chains of the human inter-α-trypsin inhibitor complex. Mol Cell Proteomics 2015; 14: 3118–3131.

  • 23

    Lamkin E, Cheng G, Calabro A, et al. Heavy chain transfer by tumor necrosis factor-stimulated gene 6 to the bikunin proteoglycan. J Biol Chem. 2015; 290: 5156–5166.

  • 24

    Higman VA, Briggs DC, Mahoney DJ, et al. A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function. J Biol Chem. 2014; 289: 5619–5634.

  • 25

    Jakab L. Connective tissue and inflammation. [Kötőszövet és inflammatio.] Orv Hetil. 2014; 155: 453–460. [Hungarian]

  • 26

    Alessandri C, Conti F, Pendolino M, et al. New autoantigens in the antiphospholipid syndrome. Autoimmun Rev. 2011; 10: 609–616.

  • 27

    Wisniewski HG, Colón E, Liublinska V, et al. TSG-6 activity as a novel biomarker of progression in knee osteoarthritis. Osteoarthritis Cartilage 2014; 22: 235–241.

  • 28

    Liao CC, Chou PL, Cheng CW, et al. Comparative analysis of novel autoantibody isotypes against citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542–556 peptide in serum from Taiwanese females with rheumatoid arthritis, primary Sjögren’s syndrome and secondary Sjögren’s syndrome in rheumatoid arthritis. J Proteomics 2016; 141: 1–11.

  • 29

    Fu G, Du Y, Chu L, et al. Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury. Exp Biol Med. 2016; 241: 1186–1194.

  • 30

    Skliris A, Happonen KE, Terpos E, et al. Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma. Eur J Immunol. 2011; 41: 437–449.

  • 31

    Brandl EJ, Lett TA, Chowdhury NI, et al. The role of the ITIH3 rs2535629 variant in antipsychotic response. Schizophr Res. 2016; 176: 131–135.

  • 32

    Liu LK, Finzel, BC. Fragment-based identification of an inducible binding site on cell surface receptor CD44 for the design of protein–carbohydrate interaction inhibitors. J Med Chem. 2014; 57: 2714–2725.

  • 33

    Patel S, Shaikh F, Devaraji V, et al. Insights into the structural perturbations of spliced variants of CD44: a modeling and simulation approach. J Biomol Struct Dyn. 2017; 35: 354–367.

  • 34

    Yoo N, Lee HR, Son JM, et al. Genkwadaphnin promotes leukocyte migration by increasing CD44 expression via PKD1/NF-κB signaling pathway. Immunol Lett. 2016; 173: 69–76.

  • 35

    Artenjak A, Locatelli I, Brelih H, et al. Immunoreactivity and avidity of IgG anti-β2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of β2-glycoprotein I. Immunol Res. 2015; 61: 35–44.

  • 36

    Richard Y, Huang C, Hudgens JW. Effects of desialylation on human α1-acid glycoprotein–ligand interactions. Biochemistry 2013; 52: 7127–7136.

  • 37

    Li L, Chaikof EL. Mechanical stress regulates syndecan-4 expression and redistribution in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002; 22: 61–68.

  • 38

    Varki A. Sialic acids in human health and disease. Trends Mol Med. 2008; 14: 351–360.

  • 39

    Terawaki S, Kitano K, Aoyama M, et al. MT1-MMP recognition by ERM proteins and its implication in CD44 shedding. Genes Cells 2015; 20: 847–859.

  • 40

    Thelin MA, Bartolini B, Axelsson J, et al. Biological functions of iduronic acid in chondroitin/dermatan sulfate. FEBS J. 2013; 280: 2431–2446.

  • 41

    Shimizukawa M, Ebina M, Narumi K, et al. Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin. Am J Physiol Lung Cell Mol Physiol. 2003; 284: L526–L532.

  • 42

    Varkoly G, Bencze J, Hortobágyi T, et al. The corneal wound healing and the extracellular matrix. [A cornealis sebgyógyulás és az extracelluláris mátrix.] Orv Hetil. 2016; 157: 995–999. [Hungarian]

  • 43

    Petrey AC, de la Motte CA. Hyaluronan, a crucial regulator of inflammation. Front Immunol. 2014; 5: 101.

  • 44

    Rugg MS, Willis AC, Mukhopadhyay D, et al. Characterization of complexes formed between TSG-6 and inter-α-inhibitor that act as intermediates in the covalent transfer of heavy chains onto hyaluronan. J Biol Chem. 2005; 280: 25674–25686.

  • 45

    Banerji S, Wright AJ, Noble M, et al. Structures of the CD44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat Struct Mol Biol. 2007; 14: 234–239.

  • 46

    Almond A. Visions and reflections (Minireview). Hyaluronan. Cell Mol Life Sci. 2007; 64: 1591–1596.

  • 47

    Petrey AC, de la Motte, CA. Thrombin cleavage of inter-α-inhibitor heavy chain 1 regulates leukocyte binding to an inflammatory hyaluronan matrix. J Biol Chem. 2016; 291: 24324–24334.

  • 48

    Baranova NS, Inforzato A, Briggs DC, et al. Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix cross-linking. J Biol Chem. 2014; 289: 30481–30498.

  • 49

    de la Motte CA, Hascall VC, Drazba J, et al. Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid:polycytidylic acid: inter-alpha-trypsin inhibitor is crucial to structure and function. Am J Pathol. 2003; 163: 121–133.

  • 50

    Guvench O. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation. Front Immunol. 2015; 6: 305.

  • 51

    Thaysen-Andersen M, Packer NH. Advances in LC-MS/MS-based glycoproteomics: getting closer to system-wide site-specific mapping of the N- and O-glycoproteome. Biochim Biophys Acta 2014; 1844: 1437–1452.

  • 52

    Hirooka T, Yoshida E, Eto K, et al. Methylmercury induces hyaluronan synthesis in cultured human brain microvascular endothelial cells and pericytes via different mechanisms. J Toxicol Sci. 2017; 42: 329–333.

  • 53

    Park Y, Jowitt TA, Day AJ, et al. Nuclear magnetic resonance insight into the multiple glycosaminoglycan binding modes of the link module from human TSG-6. Biochemistry 2016; 55: 262–276.

  • 54

    Baranova NS, Nilebäck E, Haller FM, et al. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. J Biol Chem. 2011; 286: 25675–25686.

  • 55

    Lauer ME, Cheng G, Swaidani S, et al. Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by airway smooth muscle cells. J Biol Chem. 2013; 288: 423–431.

  • 56

    Sanggaard KW, Hansen L, Scavenius C, et al. Evolutionary conservation of heavy chain protein transfer between glycosaminoglycans. Biochim Biophys Acta 2010; 1804: 1011–1019.

  • 57

    Wick G, Grundtman C, Mayerl C, et al. The immunology of fibrosis. Annu Rev Immunol. 2013; 31: 107–135.

  • 58

    Loh YP, Cheng Y, Mahata SK, et al. Chromogranin A and derived peptides in health and disease. J Mol Neurosci. 2012; 48: 347–356.

  • 59

    Noborn F, Gomez Toledo A, Sihlbom C, et al. Identification of chondroitin sulfate linkage region glycopeptides reveals prohormones as a novel class of proteoglycans. Mol Cell Proteomics 2015; 14: 41–49.

  • 60

    Lévesque H, Girard N, Maingonnat C, et al. Localization and solubilization of hyaluronan and of the hyaluronan-binding protein hyaluronectin in human normal and arteriosclerotic arterial walls. Atherosclerosis 1994; 105: 51–62.

  • 61

    Jakab L. Glycosaminoglycans, proteoglycans, atherosclerosis. [Glikozaminoglikánok, proteoglikánok, atherosclerosis.] Orv Hetil. 2004; 145: 795–803. [Hungarian]

  • 62

    Jakab L. Physiological, pathophysiological and clinical significance of chromogranins/secretogranins. [A kromograninok, szekretograninok élettani, kórélettani, klinikai szerepéről.] Orv Hetil. 2017; 158: 1092–1099. [Hungarian]

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Oct 2020 0 6 6
Nov 2020 0 21 11
Dec 2020 0 4 3
Jan 2021 0 6 8
Feb 2021 0 6 7
Mar 2021 0 14 4
Apr 2021 0 5 5