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Treatment with chondroitinase ABC alleviates bleomycin-induced pulmonary fibrosis

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Abstract

Pulmonary fibrosis is characterized by an accumulation of inflammatory cells in the lung interstitium, followed by an increased deposition of extracellular matrix. Macrophages play a vital role in this disease by mediating the progression from inflammation to fibrosis, but the mechanisms by which macrophages are retained at these sites are not fully understood. Although the transmigration of leukocytes is regulated by chemokines, glycosaminoglycans modulate the function of chemokines and the migration of leukocytes. Accordingly, we investigated the role of chondroitin sulfate proteoglycans (CSPGs) in a murine bleomycin-induced pulmonary fibrosis models. After intratracheal injection of bleomycin or saline, mice were randomized to receive one intravenous injection and continuous infusion of the CSPG-digesting enzyme chondroitinase ABC (ChABC), or vehicle, for 7 days. CSPGs were readily induced and progressively augmented after the bleomycin challenge. Although CSPGs inhibited the early CCL2-dependent recruitment of macrophages, deposited CSPGs retained macrophages in fibrotic interstitium in a CD44-dependent manner. Treatment with ChABC in vivo dramatically increased survival of the mice and reduced collagen deposition by inhibiting persistent macrophage accumulation. These results indicate a pivotal role for CSPGs in macrophage-mediated lung fibrogenesis and suggest a possible new therapeutic role for ChABC in pulmonary fibrosis.

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References

  1. F Chua J Gauldie GJ Laurent (2005) ArticleTitlePulmonary fibrosis: searching for model answers Am J Respir Cell Mol Biol 33 9–13 Occurrence Handle10.1165/rcmb.2005-0062TR Occurrence Handle1:CAS:528:DC%2BD2MXmsVSiurg%3D Occurrence Handle15964990

    Article  CAS  PubMed  Google Scholar 

  2. TJ Gross GW Hunninghake (2001) ArticleTitleIdiopathic pulmonary fibrosis N Engl J Med 345 517–525 Occurrence Handle10.1056/NEJMra003200 Occurrence Handle1:STN:280:DC%2BD3Mvns1Sqtg%3D%3D Occurrence Handle11519507

    Article  CAS  PubMed  Google Scholar 

  3. InstitutionalAuthorNameAmerican Thoracic Society (2000) ArticleTitleIdiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med 161 646–664

    Google Scholar 

  4. N Khalil O Bereznay M Sporn AH Greenberg (1989) ArticleTitleMacrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation J Exp Med 170 727–737 Occurrence Handle10.1084/jem.170.3.727 Occurrence Handle1:CAS:528:DyaL1MXlsFWgsbY%3D Occurrence Handle2475572

    Article  CAS  PubMed  Google Scholar 

  5. Y Martinet WN Rom GR Grotendorst GR Martin RG Crystal (1987) ArticleTitleExaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis N Engl J Med 317 202–209 Occurrence Handle1:STN:280:DyaL2s3lvVSrsQ%3D%3D Occurrence Handle3600711 Occurrence Handle10.1056/NEJM198707233170404

    Article  CAS  PubMed  Google Scholar 

  6. JA Lasky AR Brody (2000) ArticleTitleInterstitial fibrosis and growth factors Environ Health Perspect 108 IssueIDsuppl 4 751–762 Occurrence Handle10.2307/3454412 Occurrence Handle1:CAS:528:DC%2BD3cXms1ylsL0%3D Occurrence Handle10931794

    Article  CAS  PubMed  Google Scholar 

  7. I Nagaoka BC Trapnell RG Crystal (1990) ArticleTitleUpregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis J Clin Invest 85 2023–2027 Occurrence Handle1:CAS:528:DyaK3cXksFKlu7c%3D Occurrence Handle2347924

    CAS  PubMed  Google Scholar 

  8. HN Antoniades MA Bravo RE Avila T Galanopoulos J Neville-Golden M Maxwell M Selman (1990) ArticleTitlePlatelet-derived growth factor in idiopathic pulmonary fibrosis J Clin Invest 86 1055–1064 Occurrence Handle1:CAS:528:DyaK3cXmt1yksbs%3D Occurrence Handle2170444

    CAS  PubMed  Google Scholar 

  9. K Matsushima CG Larsen GC DuBois JJ Oppenheim (1989) ArticleTitlePurification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line J Exp Med 169 1485–1490 Occurrence Handle10.1084/jem.169.4.1485 Occurrence Handle1:CAS:528:DyaL1MXhvFSrs78%3D Occurrence Handle2926331

    Article  CAS  PubMed  Google Scholar 

  10. CM Lloyd AW Minto ME Dorf A Proudfoot TN Wells DJ Salant JC Gutierrez-Ramos (1997) ArticleTitleRANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis J Exp Med 185 1371–1380 Occurrence Handle10.1084/jem.185.7.1371 Occurrence Handle1:CAS:528:DyaK2sXisVKksbs%3D Occurrence Handle9104823

    Article  CAS  PubMed  Google Scholar 

  11. I Inoshima K Kuwano N Hamada N Hagimoto M Yoshimi T Maeyama A Takeshita S Kitamoto K Egashira N Hara (2004) ArticleTitleAnti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice Am J Physiol Lung Cell Mol Physiol 286 L1038–L1044 Occurrence Handle10.1152/ajplung.00167.2003 Occurrence Handle1:CAS:528:DC%2BD2cXkt1elsbc%3D Occurrence Handle15064241

    Article  CAS  PubMed  Google Scholar 

  12. M Suga K Iyonaga H Ichiyasu N Saita H Yamasaki M Ando (1999) ArticleTitleClinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases Eur Respir J 14 376–382 Occurrence Handle10.1034/j.1399-3003.1999.14b23.x Occurrence Handle1:STN:280:DyaK1MvktlCnsg%3D%3D Occurrence Handle10515417

    Article  CAS  PubMed  Google Scholar 

  13. M Gharaee-Kermani RE McCullumsmith IF Charo SL Kunkel SH Phan (2003) ArticleTitleCC-chemokine receptor 2 required for bleomycin-induced pulmonary fibrosis Cytokine 24 266–276 Occurrence Handle10.1016/j.cyto.2003.08.003 Occurrence Handle1:CAS:528:DC%2BD3sXovVeiurg%3D Occurrence Handle14609568

    Article  CAS  PubMed  Google Scholar 

  14. L Kjellen U Lindahl (1991) ArticleTitleProteoglycans: structures and interactions Annu Rev Biochem 60 443–475 Occurrence Handle10.1146/annurev.bi.60.070191.002303 Occurrence Handle1:CAS:528:DyaK3MXlsFeitLg%3D Occurrence Handle1883201

    Article  CAS  PubMed  Google Scholar 

  15. KR Taylor RL Gallo (2006) ArticleTitleGlycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation FASEB J 20 9–22 Occurrence Handle10.1096/fj.05-4682rev Occurrence Handle1:CAS:528:DC%2BD28XislShsg%3D%3D Occurrence Handle16394262

    Article  CAS  PubMed  Google Scholar 

  16. TM Handel Z Johnson SE Crown EK Lau AE Proudfoot (2005) ArticleTitleRegulation of protein function by glycosaminoglycans—as exemplified by chemokines Annu Rev Biochem 74 385–410 Occurrence Handle10.1146/annurev.biochem.72.121801.161747 Occurrence Handle1:CAS:528:DC%2BD2MXpsVens7c%3D Occurrence Handle15952892

    Article  CAS  PubMed  Google Scholar 

  17. CW Frevert MG Kinsella C Vathanaprida RB Goodman DG Baskin A Proudfoot TN Wells TN Wight TR Martin (2003) ArticleTitleBinding of interleukin-8 to heparan sulfate and chondroitin sulfate in lung tissue Am J Respir Cell Mol Biol 28 464–472 Occurrence Handle10.1165/rcmb.2002-0084OC Occurrence Handle1:CAS:528:DC%2BD3sXivVemtr0%3D Occurrence Handle12654635

    Article  CAS  PubMed  Google Scholar 

  18. LM Webb MU Ehrengruber I Clark-Lewis M Baggiolini A Rot (1993) ArticleTitleBinding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8 Proc Natl Acad Sci U S A 90 7158–7162 Occurrence Handle10.1073/pnas.90.15.7158 Occurrence Handle1:CAS:528:DyaK3sXmtVWntbs%3D Occurrence Handle8346230

    Article  CAS  PubMed  Google Scholar 

  19. H Kawashima N Watanabe M Hirose X Sun K Atarashi T Kimura K Shikata M Matsuda D Ogawa R Heljasvaara M Rehn T Pihlajaniemi M Miyasaka (2003) ArticleTitleCollagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1 J Biol Chem 278 13069–13076 Occurrence Handle10.1074/jbc.M212244200 Occurrence Handle1:CAS:528:DC%2BD3sXislGrtLs%3D Occurrence Handle12556525

    Article  CAS  PubMed  Google Scholar 

  20. Q Li PW Park CL Wilson WC Parks (2002) ArticleTitleMatrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury Cell 111 635–646 Occurrence Handle10.1016/S0092-8674(02)01079-6 Occurrence Handle1:CAS:528:DC%2BD38XptlGrtbs%3D Occurrence Handle12464176

    Article  CAS  PubMed  Google Scholar 

  21. J Hirose H Kawashima O Yoshie K Tashiro M Miyasaka (2001) ArticleTitleVersican interacts with chemokines and modulates cellular responses J Biol Chem 276 5228–5234 Occurrence Handle10.1074/jbc.M007542200 Occurrence Handle1:CAS:528:DC%2BD3MXhtlyjs7s%3D Occurrence Handle11083865

    Article  CAS  PubMed  Google Scholar 

  22. N Venkatesan T Ebihara PJ Roughley MS Ludwig (2000) ArticleTitleAlterations in large and small proteoglycans in bleomycin-induced pulmonary fibrosis in rats Am J Respir Crit Care Med 161 2066–2073 Occurrence Handle1:STN:280:DC%2BD3czhtFCnsw%3D%3D Occurrence Handle10852789

    CAS  PubMed  Google Scholar 

  23. ES Bensadoun AK Burke JC Hogg CR Roberts (1996) ArticleTitleProteoglycan deposition in pulmonary fibrosis Am J Respir Crit Care Med 154 1819–1828 Occurrence Handle1:STN:280:DyaK2s7isFaqtQ%3D%3D Occurrence Handle8970376

    CAS  PubMed  Google Scholar 

  24. MP Keane JA Belperio DA Arenberg MD Burdick ZJ Xu YY Xue RM Strieter (1999) ArticleTitleIFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis J Immunol 163 5686–5692 Occurrence Handle1:CAS:528:DyaK1MXntlKqsb8%3D Occurrence Handle10553099

    CAS  PubMed  Google Scholar 

  25. T Ashcroft JM Simpson V Timbrell (1988) ArticleTitleSimple method of estimating severity of pulmonary fibrosis on a numerical scale J Clin Pathol 41 467–470 Occurrence Handle10.1136/jcp.41.4.467 Occurrence Handle1:STN:280:DyaL1c3htlOltg%3D%3D Occurrence Handle3366935

    Article  CAS  PubMed  Google Scholar 

  26. M Itakura A Tokuda H Kimura S Nagai H Yoneyama N Onai S Ishikawa T Kuriyama K Matsushima (2001) ArticleTitleBlockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation J Immunol 166 2071–2079 Occurrence Handle1:CAS:528:DC%2BD3MXhtVSisb0%3D Occurrence Handle11160258

    CAS  PubMed  Google Scholar 

  27. H Yoneyama A Harada T Imai M Baba O Yoshie Y Zhang H Higashi M Murai H Asakura K Matsushima (1998) ArticleTitlePivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice J Clin Invest 102 1933–1941 Occurrence Handle1:CAS:528:DyaK1cXnvVertb8%3D Occurrence Handle9835618 Occurrence Handle10.1172/JCI4619

    Article  CAS  PubMed  Google Scholar 

  28. M Murai H Yoneyama A Harada Z Yi C Vestergaard B Guo K Suzuki H Asakura K Matsushima (1999) ArticleTitleActive participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease J Clin Invest 104 49–57 Occurrence Handle1:CAS:528:DyaK1MXktlOgsLg%3D Occurrence Handle10393698

    CAS  PubMed  Google Scholar 

  29. A Tokuda M Itakura N Onai H Kimura T Kuriyama K Matsushima (2000) ArticleTitlePivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice J Immunol 164 2745–2751 Occurrence Handle1:CAS:528:DC%2BD3cXhsVKhtbw%3D Occurrence Handle10679116

    CAS  PubMed  Google Scholar 

  30. H Yoneyama K Matsuno Y Zhang M Murai M Itakura S Ishikawa G Hasegawa M Naito H Asakura K Matsushima (2001) ArticleTitleRegulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease J Exp Med 193 35–49 Occurrence Handle10.1084/jem.193.1.35 Occurrence Handle1:CAS:528:DC%2BD3MXjtVShtA%3D%3D Occurrence Handle11136819

    Article  CAS  PubMed  Google Scholar 

  31. Y Terashima N Onai M Murai M Enomoto V Poonpiriya T Hamada K Motomura M Suwa T Ezaki T Haga S Kanegasaki K Matsushima (2005) ArticleTitlePivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis Nat Immunol 6 827–835 Occurrence Handle10.1038/ni1222 Occurrence Handle1:CAS:528:DC%2BD2MXmtlSisLo%3D Occurrence Handle15995708

    Article  CAS  PubMed  Google Scholar 

  32. NA Nelken SR Coughlin D Gordon JN Wilcox (1991) ArticleTitleMonocyte chemoattractant protein-1 in human atheromatous plaques J Clin Invest 88 1121–1127 Occurrence Handle1:CAS:528:DyaK3MXmsFeitL4%3D Occurrence Handle1843454

    CAS  PubMed  Google Scholar 

  33. JH Gong LG Ratkay JD Waterfield I Clark-Lewis (1997) ArticleTitleAn antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model J Exp Med 186 131–137 Occurrence Handle10.1084/jem.186.1.131 Occurrence Handle1:CAS:528:DyaK2sXksFais70%3D Occurrence Handle9207007

    Article  CAS  PubMed  Google Scholar 

  34. T Nagata H Kudo T Nishino Y Doi H Itoh S Fujimoto (2005) ArticleTitleIncreased immunoreactivities against endothelin-converting enzyme-1 and monocyte chemotactic protein-1 in hepatic stellate cells of rat fibrous liver induced by thioacetamide Med Mol Morphol 38 161–172 Occurrence Handle10.1007/s00795-005-0292-5 Occurrence Handle1:CAS:528:DC%2BD2MXhtVWiu7rP Occurrence Handle16170464

    Article  CAS  PubMed  Google Scholar 

  35. J Middleton S Neil J Wintle I Clark-Lewis H Moore C Lam M Auer E Hub A Rot (1997) ArticleTitleTranscytosis and surface presentation of IL-8 by venular endothelial cells Cell 91 385–395 Occurrence Handle10.1016/S0092-8674(00)80422-5 Occurrence Handle1:CAS:528:DyaK2sXnt1Cku7g%3D Occurrence Handle9363947

    Article  CAS  PubMed  Google Scholar 

  36. A Rot (1992) ArticleTitleEndothelial cell binding of NAP-1/IL-8: role in neutrophil emigration Immunol Today 13 291–294 Occurrence Handle10.1016/0167-5699(92)90039-A Occurrence Handle1:CAS:528:DyaK38Xls1yqtbc%3D Occurrence Handle1510812

    Article  CAS  PubMed  Google Scholar 

  37. A Rot (1993) ArticleTitleNeutrophil attractant/activation protein-1 (interleukin-8) induces in vitro neutrophil migration by haptotactic mechanism Eur J Immunol 23 303–306 Occurrence Handle10.1002/eji.1830230150 Occurrence Handle1:CAS:528:DyaK3sXhsVGltr4%3D Occurrence Handle8419183

    Article  CAS  PubMed  Google Scholar 

  38. A Rot E Hub J Middleton F Pons C Rabeck K Thierer J Wintle B Wolff M Zsak P Dukor (1996) ArticleTitleSome aspects of IL-8 pathophysiology. III: Chemokine interaction with endothelial cells J Leukoc Biol 59 39–44 Occurrence Handle1:CAS:528:DyaK28XnslCjtQ%3D%3D Occurrence Handle8558065

    CAS  PubMed  Google Scholar 

  39. F Zuo N Kaminski E Eugui J Allard Z Yakhini A Ben-Dor L Lollini D Morris Y Kim B DeLustro D Sheppard A Pardo M Selman RA Heller (2002) ArticleTitleGene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans Proc Natl Acad Sci U S A 99 6292–6297 Occurrence Handle10.1073/pnas.092134099 Occurrence Handle1:CAS:528:DC%2BD38XjslWnsbY%3D Occurrence Handle11983918

    Article  CAS  PubMed  Google Scholar 

  40. GP Cosgrove MI Schwarz MW Geraci KK Brown GS Worthen (2002) ArticleTitleOverexpression of matrix metalloproteinase-7 in pulmonary fibrosis Chest 121 25S–26S Occurrence Handle10.1378/chest.121.3_suppl.25S-a Occurrence Handle11893661

    Article  PubMed  Google Scholar 

  41. T Wada H Yokoyama K Furuichi KI Kobayashi K Harada M Naruto SB Su M Akiyama N Mukaida K Matsushima (1996) ArticleTitleIntervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP-1) FASEB J 10 1418–1425 Occurrence Handle1:CAS:528:DyaK28XmsVSgu7s%3D Occurrence Handle8903512

    CAS  PubMed  Google Scholar 

  42. T Wada K Furuichi N Sakai Y Iwata K Kitagawa Y Ishida T Kondo H Hashimoto Y Ishiwata N Mukaida N Tomosugi K Matsushima K Egashira H Yokoyama (2004) ArticleTitleGene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis J Am Soc Nephrol 15 940–948 Occurrence Handle10.1097/01.ASN.0000120371.09769.80 Occurrence Handle1:CAS:528:DC%2BD2cXitFWrsLo%3D Occurrence Handle15034096

    Article  CAS  PubMed  Google Scholar 

  43. TE Hardingham AJ Fosang (1992) ArticleTitleProteoglycans: many forms and many functions FASEB J 6 861–870 Occurrence Handle1:CAS:528:DyaK38Xht1egtL0%3D Occurrence Handle1740236

    CAS  PubMed  Google Scholar 

  44. JS Duffield SJ Forbes CM Constandinou S Clay M Partolina S Vuthoori S Wu R Lang JP Iredale (2005) ArticleTitleSelective depletion of macrophages reveals distinct, opposing roles during liver injury and repair J Clin Invest 115 56–65 Occurrence Handle10.1172/JCI200522675 Occurrence Handle1:CAS:528:DC%2BD2MXis1eksw%3D%3D Occurrence Handle15630444

    Article  CAS  PubMed  Google Scholar 

  45. HD Danenberg I Fishbein J Gao J Monkkonen R Reich I Gati E Moerman G Golomb (2002) ArticleTitleMacrophage depletion by clodronate-containing liposomes reduces neointimal formation after balloon injury in rats and rabbits Circulation 106 599–605 Occurrence Handle10.1161/01.CIR.0000023532.98469.48 Occurrence Handle1:CAS:528:DC%2BD38XmvVSqtLw%3D Occurrence Handle12147543

    Article  CAS  PubMed  Google Scholar 

  46. SJ Leibovich R Ross (1975) ArticleTitleThe role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum Am J Pathol 78 71–100 Occurrence Handle1:STN:280:DyaE2M%2FntFSitg%3D%3D Occurrence Handle1109560

    CAS  PubMed  Google Scholar 

  47. RC Savani Z Zhou E Arguiri S Wang D Vu CC Howe HM DeLisser (2000) ArticleTitleBleomycin-induced pulmonary injury in mice deficient in SPARC Am J Physiol Lung Cell Mol Physiol 279 L743–L750 Occurrence Handle1:CAS:528:DC%2BD3cXnsFOqsLg%3D Occurrence Handle11000135

    CAS  PubMed  Google Scholar 

  48. HN Antoniades J Neville-Golden T Galanopoulos RL Kradin AJ Valente DT Graves (1992) ArticleTitleExpression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis Proc Natl Acad Sci U S A 89 5371–5375 Occurrence Handle10.1073/pnas.89.12.5371 Occurrence Handle1:CAS:528:DyaK38XksVGksLY%3D Occurrence Handle1608944

    Article  CAS  PubMed  Google Scholar 

  49. N Sakai T Wada K Furuichi K Shimizu S Kokubo A Hara J Yamahana T Okumura K Matsushima H Yokoyama S Kaneko (2006) ArticleTitleMCP-1/CCR2-dependent loop for fibrogenesis in human peripheral CD14-positive monocytes J Leukoc Biol 79 555–563 Occurrence Handle10.1189/jlb.0305127 Occurrence Handle1:CAS:528:DC%2BD28XisFKnu7g%3D Occurrence Handle16415174

    Article  CAS  PubMed  Google Scholar 

  50. E Vachon R Martin J Plumb V Kwok RW Vandivier M Glogauer A Kapus X Wang CW Chow S Grinstein GP Downey (2006) ArticleTitleCD44 is a phagocytic receptor Blood 107 4149–4158 Occurrence Handle10.1182/blood-2005-09-3808 Occurrence Handle1:CAS:528:DC%2BD28XkvFWgs7k%3D Occurrence Handle16455948

    Article  CAS  PubMed  Google Scholar 

  51. K Svee J White P Vaillant J Jessurun U Roongta M Krumwiede D Johnson C Henke (1996) ArticleTitleAcute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44 J Clin Invest 98 1713–1727 Occurrence Handle1:CAS:528:DyaK28XmtlOgtb4%3D Occurrence Handle8878421

    CAS  PubMed  Google Scholar 

  52. T Murai N Sougawa H Kawashima K Yamaguchi M Miyasaka (2004) ArticleTitleCD44-chondroitin sulfate interactions mediate leukocyte rolling under physiological flow conditions Immunol Lett 93 163–170 Occurrence Handle10.1016/j.imlet.2004.03.013 Occurrence Handle1:CAS:528:DC%2BD2cXktF2lsrs%3D Occurrence Handle15158613

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Preventive Medicine and SORST, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Yoshiro Kai, Hiroyuki Yoneyama & Kouji Matsushima

  2. Second Department of Internal Medicine, Nara Medical University, Nara, Japan

    Yoshiro Kai, Kaoru Hamada & Hiroshi Kimura

  3. Laboratory of Stem Cell Dynamism, Stelic Institute of Regenerative Medicine, 1-9-15 Higashi-Azabu, Minato-ku, Tokyo, 106-0044, Japan

    Hiroyuki Yoneyama & Jun Koyama

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  1. Yoshiro Kai
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Correspondence to Hiroyuki Yoneyama.

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Kai, Y., Yoneyama, H., Koyama, J. et al. Treatment with chondroitinase ABC alleviates bleomycin-induced pulmonary fibrosis. Med Mol Morphol 40, 128–140 (2007). https://doi.org/10.1007/s00795-007-0370-y

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