Skip to main content

Advertisement

Log in

Increased immunoreactivities against endothelin-converting enzyme-1 and monocyte chemotactic protein-1 in hepatic stellate cells of rat fibrous liver induced by thioacetamide

  • ORIGINAL PAPER
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

The progression of rat liver fibrosis induced by intraperitoneal administration of thioacetamide (TAA) was evaluated by immunocytochemistry using anti-α-smooth muscle actin (α-SMA), antiendothelin-converting enzyme (ECE)-1, and anti-monocyte chemotactic protein (MCP)-1 antibodies. The fibrous septal spaces gradually increased after administration of TAA, and pseudolobules were established in the 7-week TAA-treated groups. Immunoreactivities against α-SMA were not detected in hepatic stellate cells (HSCs) of the control group without TAA treatment, although they were observed in the HSCs around the fibrous septal spaces in all TAA-treated groups, indicating that activation of HSCs occurs during the establishment of pseudolobules. Immunoreactivities against ECE-1 and MCP-1 were seen in such HSCs of the TAA-treated groups, but few or no immunoreactivities were detected in the HSCs of the control group. The most significant increase in the ECE-1 immunoreactivities was detected in the 1-week TAA-treated group, whereas that in MCP-1 was observed in the 7-week TAA-treated group. The present immunocytochemistry indicated a difference in the accelerated expression period between immunoreactivities against ECE-1 and MCP-1 in the HSCs during the progression of TAA-induced liver fibrosis, suggesting that ECE-1 is involved in the early phase of liver fibrosis and that MCP-1 plays a role during the later phase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. G Ramadori (1991) ArticleTitleThe stellate cell (Ito-cell, fat storing cell, lipocyte, perisinusoidal cell) of the liver. New insights into pathophysiology of an intriguing cell Virchow Arch B Cell Pathol Mol Pathol 61 147–158

    Google Scholar 

  2. SL Friedman (1993) ArticleTitleSeminars in Medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies N Engl J Med 328 1828–1835 Occurrence Handle10.1056/NEJM199306243282508 Occurrence Handle8502273

    Article  PubMed  Google Scholar 

  3. H Reynaert MG Thompson T Thomas A Geerts (2002) ArticleTitleHepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension Gut 50 571–581 Occurrence Handle10.1136/gut.50.4.571 Occurrence Handle11889082

    Article  PubMed  Google Scholar 

  4. Y Tanaka T Nouchi M Yamane T Irie H Miyakawa C Sato F Marumo (1991) ArticleTitlePhenotypic modulation in lipocytes in experimental liver fibrosis J Pathol 164 273–278 Occurrence Handle10.1002/path.1711640314 Occurrence Handle1890552

    Article  PubMed  Google Scholar 

  5. H Enzan H Himeno S Iwamura T Saibara S Onishi Y Yamamoto H Hara (1994) ArticleTitleImmunohistochemical identification of Ito cells and their myofibroblastic transformation in adult human liver Virchows Arch 424 249–256 Occurrence Handle10.1007/BF00194608 Occurrence Handle8186890

    Article  PubMed  Google Scholar 

  6. ML Hautekeete A Geerts (1997) ArticleTitleThe hepatic stellate (Ito) cell: its role in human liver disease Virchows Arch 430 195–207 Occurrence Handle10.1007/BF01324802 Occurrence Handle9099976

    Article  PubMed  Google Scholar 

  7. T Ueno M Sata R Sakata T Torimura M Sakamoto H Sugawara K Tanikawa (1997) ArticleTitleHepatic stellate cells and intralobular innervation in human liver cirrhosis Hum Pathol 28 953–959 Occurrence Handle10.1016/S0046-8177(97)90011-3 Occurrence Handle9269832

    Article  PubMed  Google Scholar 

  8. T Takahara Y Nakayama H Itoh C Miyabayashi A Watanabe H Sasaki K Inoue Y Muragaki A Ooshima (1992) ArticleTitleExtracellular matrix formation in piecemeal necrosis: immunoelectron microscopic study Liver 12 368–380 Occurrence Handle1335106

    PubMed  Google Scholar 

  9. H Senoo (2004) ArticleTitleStructure and function of hepatic stellate cells Med Electron Microsc 37 3–15 Occurrence Handle10.1007/s00795-003-0230-3 Occurrence Handle15057600

    Article  PubMed  Google Scholar 

  10. JE Hines SJ Johnson AD Burt (1993) ArticleTitleIn vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury Am J Pathol 142 511–518 Occurrence Handle8434646

    PubMed  Google Scholar 

  11. M Ide J Yamate Y Machida O Sawamoto M Nakanishi M Kuwamura T Kotani S Sakuma (2002) ArticleTitleMacrophage populations, myofibroblastic cells, and extracellular matrix accumulation in chronically-developing rat liver cirrhosis induced by repeated injection of thioacetamide J Toxicol Pathol 15 19–29 Occurrence Handle10.1293/tox.15.19

    Article  Google Scholar 

  12. M Yanagisawa H Kurihara S Kimura Y Tomobe M Kobayashi Y Mitsui Y Yazaki K Goto T Masaki (1988) ArticleTitleA novel potent vasoconstrictor peptide produced by vascular endothelial cells Nature (Lond) 332 411–415 Occurrence Handle10.1038/332411a0

    Article  Google Scholar 

  13. GA Ramm AC Hoskins SA Greco TN Pereira PJ Lewindon (2004) ArticleTitleSignals for hepatic figrogenesis in pediatric cholestatic liver disease: review and hypothesis Comp Hepatol 3 S5 Occurrence Handle10.1186/1476-5926-2-S1-S5 Occurrence Handle14960157

    Article  PubMed  Google Scholar 

  14. H Fukushige Y Doi H Kudo K Kayashima H Kiyonaga T Nagata H Itoh S Fujimoto (2000) ArticleTitleSynthesis and receptor sites of endothelin-1 in the rat liver vasculature Anat Rec 259 437–445 Occurrence Handle10.1002/1097-0185(20000801)259:4<437::AID-AR70>3.0.CO;2-8 Occurrence Handle10903535

    Article  PubMed  Google Scholar 

  15. H Yokomori M Oda M Ogi Y Kamegaya N Tsukada M Nakamura H Ishii (2001) ArticleTitleEnhanced expression of endothelin receptor subtypes in cirrhotic rat liver Liver 21 114–122 Occurrence Handle10.1034/j.1600-0676.2001.021002114.x Occurrence Handle11318980

    Article  PubMed  Google Scholar 

  16. X Shi-Wen CP Denton MR Dashwood AM Holmes G Bou-Gharios JD Pearson CM Black DJ Abraham (2001) ArticleTitleFibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1 J Invest Dermatol 116 417–425 Occurrence Handle10.1046/j.1523-1747.2001.01256.x Occurrence Handle11231316

    Article  PubMed  Google Scholar 

  17. SL Friedman (2000) ArticleTitleMolecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury J Biol Chem 275 2247–2250 Occurrence Handle10.1074/jbc.275.4.2247 Occurrence Handle10644669

    Article  PubMed  Google Scholar 

  18. M Pinzani S Milani R De Franco C Grappone A Caligiuri A Gentilini C Tosti-Guerra M Maggi P Failli C Ruocco P Gentilini (1996) ArticleTitleEndothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells Gastroenterology 110 534–548 Occurrence Handle10.1053/gast.1996.v110.pm8566602 Occurrence Handle8566602

    Article  PubMed  Google Scholar 

  19. DC Rockey L Fouassier JJ Chung A Carayon P Vallee C Rey C Housset (1998) ArticleTitleCellular localization of endothelin-1 and increased production in liver injury in the rat: potential for autocrine and paracrine effects on stellate cells Hepatology 27 472–480 Occurrence Handle10.1002/hep.510270222 Occurrence Handle9462646

    Article  PubMed  Google Scholar 

  20. C Housset DC Rockey DM Bissell (1993) ArticleTitleEndothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1 Proc Natl Acad Sci USA 90 9266–9270 Occurrence Handle8415690

    PubMed  Google Scholar 

  21. TJ Opgenorth JR Wu-Wong K Shiosaki (1992) ArticleTitleEndothelin-converting enzymes FASEB J 6 2653–2659 Occurrence Handle1612289

    PubMed  Google Scholar 

  22. L Muller A Barret E Etienne R Meidan O Valdenaire P Corvol C Tougard (2003) ArticleTitleHeterodimerization of endothelin-converting enzyme-1 isoforms regulates the subcellular distribution of this metalloprotease J Biol Chem 278 545–555 Occurrence Handle10.1074/jbc.M208949200 Occurrence Handle12393864

    Article  PubMed  Google Scholar 

  23. R Corder S Barker (1999) ArticleTitleThe expression of endothelin-1 and endothelin-converting enzyme-1 (ECE-1) are independently regulated in bovine aortic endothelial cells J Cardiovasc Pharmacol 33 671–677 Occurrence Handle10.1097/00005344-199904000-00023 Occurrence Handle10218741

    Article  PubMed  Google Scholar 

  24. R Shao W Yan DC Rockey (1999) ArticleTitleRegulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during wound healing J Biol Chem 274 3228–3234 Occurrence Handle10.1074/jbc.274.5.3228 Occurrence Handle9915864

    Article  PubMed  Google Scholar 

  25. MJ Czaja A Geerts J Xu P Schmiedeberg Y Ju (1994) ArticleTitleMonocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease J Leukoc Biol 55 120–126 Occurrence Handle8283136

    PubMed  Google Scholar 

  26. CD Dijkstra EA Döpp P Joling G Kraal (1985) ArticleTitleThe heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3 Immunology 54 589–599 Occurrence Handle3882559

    PubMed  Google Scholar 

  27. M Naito G Hasegawa Y Ebe T Yamamoto (2004) ArticleTitleDifferentiation and function of Kupffer cells Med Electron Microsc 37 16–28 Occurrence Handle10.1007/s00795-003-0228-x Occurrence Handle15057601

    Article  PubMed  Google Scholar 

  28. AM Gressner (1996) ArticleTitleTransdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis Kidney Int 54 S39–S45

    Google Scholar 

  29. S Vogl U Junker H Vogelsang R Dargel (1997) ArticleTitleMacrophages from rat livers with micronodular and macronodular cirrhosis differ with respect to mediator release and DNA-synthesis J Hepatol 26 1093–1103 Occurrence Handle10.1016/S0168-8278(97)80118-3 Occurrence Handle9186840

    Article  PubMed  Google Scholar 

  30. MI Torres-López MI Fernández L Fontana A Gil A Ríos (1996) ArticleTitleInfluence of dietary nucleotides on liver structural recovery and hepatocyte binuclearity in cirrhosis induced by thioacetamide Gut 38 260–264 Occurrence Handle8801208

    PubMed  Google Scholar 

  31. MI Torres MI Fernández A Gil A Ríos (1998) ArticleTitleDietary nucleotides have cytoprotective properties in rat liver damaged by thioacetamide Life Sci 62 13–22 Occurrence Handle10.1016/S0024-3205(97)01033-3 Occurrence Handle9444963

    Article  PubMed  Google Scholar 

  32. F Marra AJ Valente M Pinzani HE Abboud (1993) ArticleTitleCultured human liver fat-storing cells produce monocyte chemotactic protein-1: regulation by proinflammatory cytokines J Clin Invest 92 1674–1680 Occurrence Handle8408620

    PubMed  Google Scholar 

  33. F Marra R DeFranco C Grappone S Milani S Pastacaldi M Pinzani RG Romanelli G Laffi P Gentilini (1998) ArticleTitleIncreased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration Am J Pathol 152 423–430 Occurrence Handle9466568

    PubMed  Google Scholar 

  34. F Marra RG Romanelli C Giannini P Failli S Pastacaldi MC Arrighi M Pinzani G Laffi P Montalto P Gentilini (1999) ArticleTitleMonocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells Hepatology 29 140–148 Occurrence Handle10.1002/hep.510290107 Occurrence Handle9862860

    Article  PubMed  Google Scholar 

  35. Y Doi H Kudo T Nishino O Yamamoto T Nagata S Nara M Morita S Fujimoto (2002) ArticleTitleEnhanced expression of endothelin-1 and endothelin-converting enzyme-1 acute hypoxic rat aorta Histol Histopathol 17 97–105 Occurrence Handle11813889

    PubMed  Google Scholar 

  36. IW Mclean PK Nakane (1974) ArticleTitlePeriodate-lysine-paraformaldehyde fixative: a new fixation for immunoelectron microscopy J Histochem Cytochem 22 1077–1083 Occurrence Handle4374474

    PubMed  Google Scholar 

  37. H Enzan Y Hayashi E Miyazaki K Naruse R Tao N Kuroda H Nakayama H Kiyoku M Hiroi T Saibara (1999) Morphological aspects of hepatic fibrosis and Ito cells (hepatic stellate cells), with special reference to their myofibroblastic transformation K Tanikawa T Ueno (Eds) Liver diseases and hepatic sinusoidal cells Springer Tokyo 219–231

    Google Scholar 

  38. A Azouz MS Razzaque M El-Hallak T Taguchi (2004) ArticleTitleImmunoinflammatory responses and fibrogenesis Med Electron Microsc 37 141–148 Occurrence Handle10.1007/s00795-004-0255-2 Occurrence Handle15449105

    Article  PubMed  Google Scholar 

  39. H Nakatsukasa RP Evarts C-C Hsia SS Thorgeirsson (1990) ArticleTitleTransforming growth factor-β1 and type I procollagen transcripts during regeneration and early fibrosis of rat liver Lab Invest 63 171–180 Occurrence Handle2381163

    PubMed  Google Scholar 

  40. R Shao Z Shi PJ Gotwals VE Koteliansky J George DC Rockey (2003) ArticleTitleCell and molecular regulation of endothelin-1 production during hepatic wound healing Mol Biol Cell 14 2327–2341

    Google Scholar 

  41. Y Doi H Kudo O Yamamoto K Hamasaki M Yoshizuka S Fujimoto (2002) ArticleTitleEnhancement of immunoreactivity for endothelin-1 and endothelin-converting enzyme-1 in the cadmium-treated rat thoracic aorta Virchows Arch 441 179–186 Occurrence Handle10.1007/s00428-001-0596-3 Occurrence Handle12189509

    Article  PubMed  Google Scholar 

  42. T Ota M Tamura A Osajima Y Doi H Kudo H Anai M Miyazaki T Nishino Y Nakashima (2002) ArticleTitleExpression of monocyte chemoattractant protein-1 in proximal tubular epithelial cells in a rat model of progressive kidney failure J Lab Clin Med 140 43–51 Occurrence Handle10.1067/mlc.2002.125215 Occurrence Handle12080327

    Article  PubMed  Google Scholar 

  43. M Gharaee-Kermani EM Denholm SH Phan (1996) ArticleTitleCostimulation of fibroblast collagen and transforming growth factor β1 gene expression by monocyte chemoattractant protein-1 via specific receptors J Biol Chem 271 17779–17784 Occurrence Handle10.1074/jbc.271.30.17779 Occurrence Handle8663511

    Article  PubMed  Google Scholar 

  44. CM Lloyd AW Minto ME Dorf A Proudfoot TNC Wells DJ Salant J-C 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 Handle9104823

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takahisa Nagata.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagata, T., Kudo, H., Nishino, T. et al. Increased 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 (2005). https://doi.org/10.1007/s00795-005-0292-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-005-0292-5

Key words

Navigation