Matrix metalloproteinase-10 expression is induced during hepatic injury and plays a fundamental role in liver tissue repair
Oihane Garcia-Irigoyen
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Both authors made equal contribution.Search for more papers by this authorSimone Carotti
Centre for Integrated biomedical Research (CIR), Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome, Italy
Both authors made equal contribution.Search for more papers by this authorMaria U. Latasa
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorIker Uriarte
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaite G. Fernández-Barrena
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaria Elizalde
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorRaquel Urtasun
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorUmberto Vespasiani-Gentilucci
Liver Unit, University Campus Bio-Medico of Rome, Rome, Italy
Search for more papers by this authorSergio Morini
Centre for Integrated biomedical Research (CIR), Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome, Italy
Search for more papers by this authorJesús M. Banales
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute-Donostia University Hospital, IKERBASQUE, University of Basque Country, San Sebastián, Spain
Search for more papers by this authorWilliam C. Parks
Center for Lung Biology, University of Washington, Seattle, WA, USA
Search for more papers by this authorJose A. Rodriguez
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorJosune Orbe
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorJesús Prieto
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorJose A. Páramo
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorCarmen Berasain
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Both authors share senior authorship.Search for more papers by this authorCorresponding Author
Matías A. Ávila
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Both authors share senior authorship.Correspondence
Dr. Matias A Ávila , Division of Hepatology and Gene Therapy, CIMA, Avda, Pio XII, n55, 31008 Pamplona, Spain
Tel: +34 948 194700
Fax: +34 948 194717
e-mails: [email protected]
Search for more papers by this authorOihane Garcia-Irigoyen
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Both authors made equal contribution.Search for more papers by this authorSimone Carotti
Centre for Integrated biomedical Research (CIR), Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome, Italy
Both authors made equal contribution.Search for more papers by this authorMaria U. Latasa
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorIker Uriarte
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaite G. Fernández-Barrena
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaria Elizalde
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorRaquel Urtasun
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorUmberto Vespasiani-Gentilucci
Liver Unit, University Campus Bio-Medico of Rome, Rome, Italy
Search for more papers by this authorSergio Morini
Centre for Integrated biomedical Research (CIR), Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome, Italy
Search for more papers by this authorJesús M. Banales
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute-Donostia University Hospital, IKERBASQUE, University of Basque Country, San Sebastián, Spain
Search for more papers by this authorWilliam C. Parks
Center for Lung Biology, University of Washington, Seattle, WA, USA
Search for more papers by this authorJose A. Rodriguez
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorJosune Orbe
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorJesús Prieto
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorJose A. Páramo
Centro de Investigación Médica Aplicada (CIMA), Division of Cardiovascular Sciences, Universidad de Navarra, Pamplona, Spain
Search for more papers by this authorCarmen Berasain
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Both authors share senior authorship.Search for more papers by this authorCorresponding Author
Matías A. Ávila
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
Both authors share senior authorship.Correspondence
Dr. Matias A Ávila , Division of Hepatology and Gene Therapy, CIMA, Avda, Pio XII, n55, 31008 Pamplona, Spain
Tel: +34 948 194700
Fax: +34 948 194717
e-mails: [email protected]
Search for more papers by this authorAbstract
Background & Aims
Upon tissue injury, the liver mounts a potent reparative and regenerative response. A role for proteases, including serine and matrix metalloproteinases (MMPs), in this process is increasingly recognized. We have evaluated the expression and function of MMP10 (stromelysin-2) in liver wound healing and regeneration.
Methods
The hepatic expression of MMP10 was examined in two murine models: liver regeneration after two-thirds partial hepatectomy (PH) and bile duct ligation (BDL). MMP10 was detected in liver tissues by qPCR, western blotting and immunohistochemistry. The effect of growth factors and toll-like receptor 4 (TLR4) agonists on MMP10 expression was studied in cultured parenchymal and biliary epithelial cells and macrophages respectively. The role of MMP10 was evaluated by comparing the response of Mmp10+/+ and Mmp10−/− mice to PH and BDL. The intrahepatic turnover of the extracellular matrix proteins fibrin (ogen) and fibronectin was examined.
Results
MMP10 mRNA was readily induced after PH and BDL. MMP10 protein was detected in hepatocytes, cholangiocytes and macrophages. In cultured liver epithelial cells, MMP10 expression was additively induced by transforming growth factor-β and epidermal growth factor receptor ligands. TLR4 ligands also stimulated MMP10 expression in macrophages. Lack of MMP10 resulted in increased liver injury upon PH and BDL. Resolution of necrotic areas was impaired, and Mmp10−/− mice showed increased fibrogenesis and defective turnover of fibrin (ogen) and fibronectin.
Conclusions
MMP10 expression is induced during mouse liver injury and participates in the hepatic wound healing response. The profibrinolytic activity of MMP10 may be essential in this novel hepatoprotective role.
Supporting Information
| Filename | Description |
|---|---|
| liv12337-sup-0001-FigS1.tifimage/tif, 1.2 MB | Fig. S1. Circulating transaminases levels in wild type and Mmp10−/− mice after partial hepatectomy. |
| liv12337-sup-0002-FigS2.tifimage/tif, 1.2 MB | Fig. S2. Circulating transaminases levels in wild type and Mmp10−/− mice after bile duct ligation. |
| liv12337-sup-0003-TableS1.docxWord document, 12.1 KB | Table S1. Primers used for qPCR. |
| liv12337-sup-0004-FigureS1-S2-Legends.docxWord document, 10.2 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2004; 5: 836–47.
- 2Michalopoulos GK. Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol 2010; 176: 2–13.
- 3Böhm F, Köhler UA, Speicher T, Werner S. Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med 2010; 2: 294–305.
- 4Uriarte I, Fernandez-Barrena MG, Monte MJ, et al. Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice. Gut 2013; 62: 899–910.
- 5Kim TH, Mars WM, Stolz DB, Petersen BE, Michalopoulos GK. Extracellular matrix remodelling at the early stages of liver regeneration in the rat. Hepatology 1997; 26: 896–904.
- 6Mohammed FF, Khokha R. Thinking outside the cell: proteases regulate hepatocyte division. Trends Cell Biol 2005; 15: 555–63.
- 7Bezerra JA, Bugge TH, Melin-Aldana H, et al. Plasminogen deficiency leads to impaired remodelling after a toxic injury to the liver. Proc Natl Acad Sci USA 1999; 96: 15143–8.
- 8Neubauer K, Knittel T, Armbrust T, Ramadori G. Accumulation and cellular localization of fibrinogen/fibrin during short-term and long-term rat liver injury. Gastroenterology 1995; 108: 1124–36.
- 9Tsujimoto I, Moriya K, Sakai K, Dickneite G, Sakai T. Critical role of factor XIII in the initial stages of carbon tetrachloride-induced adult liver remodelling. Am J Pathol 2011; 179: 3011–9.
- 10Roselli HT, Su M, Washington K, et al. Liver regeneration is transiently impaired in urokinase-deficient mice. Am J Physiol Gastrointest Liver Physiol 1998; 275: G1472–9.
- 11Ng VL, Sabla G, Melin-Aldana H, et al. Plasminogen deficiency results in poor clearance of non-fibrin matrix and persistent activation of hepatic stellate cells after an acute injury. J Hepatol 2001; 35: 781–9.
- 12Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem 2009; 284: 12917–23.
- 13Kim TH, Mars WM, Stolz DB, Michalopoulos GK. Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration. Hepatology 2000; 30: 75–82.
- 14Knittel T, Mehde M, Grundmann A, et al. Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat. Histochem Cell Biol 2000; 113: 443–53.
- 15Hemmann S, Graf J, Roderfeld M, Roeb E. Expression of MMPs and TIMPs in liver fibrosis – a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 2007; 46: 955–75.
- 16Uchinami H, Seki E, Brenner DA, D'Armiento J. Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis. Hepatology 2006; 44: 420–9.
- 17Fallowfield JA, Mizuno M, Kendall TJ, et al. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine fibrosis. J Immunol 2007; 178: 5288–95.
- 18Olle EW, Ren X, McClintock SD, et al. Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice. Hepatology 2006; 44: 540–9.
- 19Yan C, Zhou L, Han YP. Contribution of hepatic stellate cell and matrix metalloproteinase 9 in acute liver failure. Liver Int 2008; 28: 959–71.
- 20Krampert M, Bloch W, Sasaki T, et al. Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin. Mol Biol Cell 2004; 15: 5242–54.
- 21Koller FL, Dozier EA, Nam KT, et al. Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia. Lab Invest 2012; 92: 1749–59.
- 22Rodriguez JA, Orbe J, Martinez de Lizarrondo s, et al. Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli. Front Biosci 2008; 13: 2916–21.
- 23Nakamura H, Fujii Y, Ohuchi E, Yamamoto E, Okada Y. Activation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases. Eur J Biochem 1998; 253: 67–75.
- 24Orbe J, Barrenetxe J, Rodriguez JA, et al. Matrix metalloproteinase-10 effectively reduces infarct size in experimental stroke by enhancing fibrinolysis via a thrombin-activatable fibrinolysis inhibitor-mediated mechanism. Circulation 2011; 124: 2909–19.
- 25Bezerra JA, Currier AR, Melin-Aldana H, et al. Plasminogen activators direct reorganization of the liver lobule alter acute injury. Am J Pathol 2001; 158: 921–9.
- 26Kassim SY, Gharib SA, Mecham BH, et al. Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa. Infect Immun 2007; 75: 564050.
- 27Berasain C, García-Trevijano ER, Castillo J, et al. Amphiregulin: an early trigger of liver regeneration. Gastroenterology 2005; 128: 424–32.
- 28Mitchell C, Mahrouf-Yorgov M, Mayeuf A, et al. Overexpression of Bcl-2 in hepatocytes protects against injury but does not attenuate fibrosis in a mouse model of chronic cholestatic liver disease. Lab Invest 2011; 91: 273–82.
- 29Perugorría MJ, Latasa MU, Nicou A, et al. The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis. Hepatology 2008; 48: 1251–61.
- 30Rudich N, Zamir G, Pappo O, et al. Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut. Liver Int 2009; 29: 1273–84.
- 31Fernández-Barrena MG, Monte MJ, Latasa MU, et al. Lack of Abcc3 expression impairs bile-acid induced liver growth and delays hepatic regeneration after partial hepatectomy in mice. J Hepatol 2012; 56: 367–73.
- 32Latasa MU, Gil-Puig C, Fernández-Barrena MG, et al. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice. PLoS ONE 2010; 5: e15690.
- 33Lasarte JJ, Casares N, Gorraiz M, et al. The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J Immunol 2007; 178: 748–56.
- 34Berasain C, García-Trevijano ER, Castillo J, et al. Novel role for amphiregulin in protection from liver injury. J Biol Chem 2005; 280: 19012–20.
- 35Luyendyk JP, Cantor GH, Kirchofer D, et al. Tissue factor-dependent coagulation contributes to α-naphthylisothiocyanate-induced cholestatic liver injury in mice. Am J Physiol Gastrointest Liver Physiol 2009; 296: G840–9.
- 36Rabilloud T, Adessi C, Giraudel A, Lunardi J. Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 1997; 18: 307–16.
- 37Berasain C, Hevia H, Fernández-Irigoyen J, et al. Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma. Biochim Biophys Acta 2004; 1690: 276–84.
- 38Gujral JS, Farhood A, Bajt ML, Jaeschke H. Neutrophils aggravate acute liver injury during obstructive cholestasis. Hepatology 2003; 38: 355–63.
- 39Canbay A, Guicciardi ME, Higuchi H, et al. Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. J Clin Invest 2003; 112: 152–9.
- 40Österreicher CH, Trauner M. Animal models of biliary tract injury. Curr Opin Gastroenterol 2012; 28: 239–43.
- 41Wilkins-Port C, Ye Q, Mazurkiewicz JE, Higgins PJ. TGF-β1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodelling axis: role for PAI-1. Cancer Res 2009; 69: 4081–91.
- 42Ishikawa F, Miyoshi H, Nose K, Shibanuma M. Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation of class IIa HDACs. Oncogene 2009; 29: 909–19.
- 43Seki E, De Minicis S, Inokuchi S, et al. CCR2 promotes hepatic fibrosis in mice. Hepatology 2009; 56: 185–97.
- 44Berasasin C, Castillo J, Prieto J, Avila MA. New molecular targets for hepatocellular carcinoma: the ErbB1 signaling system. Liver Int 2007; 27: 174–85.
- 45Isayama F, Hines IN, Kremer M, et al. LPS signalling enhances hepatic fibrogenesis caused by experimental cholestasis in mice. Am J Physiol Gastrointest Liver Physiol 2006; 290: G1318–28.
- 46Huang WC, Sala-Newby GB, Susana A, Johnson JI, Newby AC. Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-kappa B. PLoS One 2012; 7: e42507.
- 47Murray MY, Birkland TP, Howe JD, et al. Macrophage migration and invasion is regulated by MMP10 expression. PLoS One 2013; 8: e63555.
- 48Kubes P, Mehal WZ. Sterile inflammation in the liver. Gastroenterology 2012; 143: 1158–72.
- 49Chang ML, Chen JC, Alonso CR, Kornblihtt AR, Bissell DM. Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver. Proc Natl Acad Sci USA 2004; 101: 18093–8.
- 50Okamura Y, Watari M, Jerud ES, et al. The extra domain A of fibronectin activates toll-like receptor 4. J Biol Chem 2001; 276: 10229–33.
- 51Treiber M, Neuhöfer P, Anetsberger E, et al. Myeloid, but not pancreatic, RelA/p65 is requiered for fibrosis in a mouse model of chronic pancreatitis. Gastroenterology 2011; 141: 1473–85.
- 52Strey CW, Markiewski M, Mastellos D, et al. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med 2003; 198: 913–23.
- 53Mitchell C, Willenbring H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat Protocols 2008; 3: 1167–70.
- 54Fickert P, Trauner M, Fuchsbichler A, et al. Oncosis represents the main type of cell death in mouse models of cholestasis. J Hepatol 2005; 42: 378–89.
- 55Wagner M, Fickert P, Zollner G, et al. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 2003; 125: 825–38.
- 56Beier JI, Luyendyk JP, Guo L, et al. Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide-induced liver injury caused by ethanol in mice. Hepatology 2009; 49: 1545–53.
- 57Weeerasinghe SVW, Moons D, Altshuler PJ, Shah YM, Omary MB. Fibrinogen-γ proteolysis and solubility dynamics during apoptotic mouse liver injury: heparin prevents and treats liver damage. Hepatology 2011; 53: 1323–32.
- 58Moriya K, Sakai K, Yan MH, Sakai T. Fibronectin is essential for survival but is dispensable for proliferation of hepatocytes in acute liver injury in mice. Hepatology 2012; 56: 311–21.
- 59Vierkotten S, Muether PS, Fauser S. Overexpression of HTRA1 leads to ultrastructural changes in the elastic layer of Bruch's membrane via cleavage of extracellular matrix components. PLoS One 2011; 6: e22959.
- 60Horowitz JC, Rogers DS, Simon RS, Sisson TH, Thannickal VJ. Plasminogen activation-induced pericellular fibronectin proteolysis promotes fibroblast apoptosis. Am J Respir Cell Mol Biol 2008; 38: 78–87.
- 61Montero I, Orbe J, Varo N, et al. C-Reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells. J Am Coll Cardiol 2006; 47: 1369–78.
- 62Gill SE, Parks WC. Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol 2008; 40: 1334–47.
- 63Berasain C, Perugorria MJ, Latasa MU, et al. The epidermal growth factor receptor: a link between inflammation and liver cancer. Exp Biol Med 2009; 234: 713–25.
- 64Ruiz PA, Jarai G. Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. J Biol Chem 2011; 286: 12912–23.
- 65Bergheim I, Guo L, Davis MA, Duveau I, Arteel GE. Critical role of plasminogen activator inhibitor-1 in cholestatic liver injury and fibrosis. J Pharmacol Exp Ther 2006; 316: 592–600.
- 66Luyendyk JP, Mackman N, Sullivan BP. Role of fibrinogen and protease-activated receptors in acute xenobiotic-induced cholestatic liver injury. Toxicol Sci 2011; 119: 233–43.
- 67Anstee QM, Goldin RD, Wright M, et al. Coagulation status modulates murine hepatic fibrogenesis: implications for the development of novel therapies. J Thromb Haemost 2008; 6: 1336–43.
- 68Si-Tayeb K, Monvoisin A, Mazzocco C, et al. Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol 2006; 169: 1390–401.
- 69Eguchi T, Kubota S, Kawata K, et al. Novel transcription factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene. Mol Cell Biol 2008; 28: 2391–413.
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