, Volume 185, Issue 1, pp 31–37 | Cite as

RETRACTED ARTICLE: Coexpression of HSP47 Gene and Type I and Type III Collagen Genes in LPS-Induced Pulmonary Fibrosis in Rats

  • Satoshi Hagiwara
  • Hideo Iwasaka
  • Shigekiyo Matsumoto
  • Takayuki Noguchi
  • Hidekatsu Yoshioka


Diffuse alveolar damage is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). A significant proportion of ARDS survivors have residual pulmonary fibrosis and compromised pulmonary function. On the other hand, heat shock protein 47 (HSP47) is a collagen-binding stress protein that is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen in living cells. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines. We examined the expression of HSP47 mRNA and protein during the progression of lipopolysaccharide (LPS)-induced ARDS in rat lung. Male Wistar rats were randomly divided into two groups: a control group with instillation of 0.9% NaCl solution alone, and a LPS group with instillation of LPS dissolved in 0.9% NaCl solution (10 mg/kg). Histologic changes thereafter appeared in the LPS-treated rats. Northern blot analysis revealed the expression of HSP47 mRNA to be markedly induced during the progression of lung damage in parallel with type I and type III collagen mRNA. These results suggest that the upregulation of HSP47 and collagen may play an important role in the fibrotic process of LPS-induced ARDS lung.


Acute respiratory distress syndrome (ARDS) Collagen Heat shock protein 47 Lipopolysaccharide Pulmonary fibrosis 



The authors thank Professor K. Nagata (Kyoto University, Japan) for kindly donating the plasmid with the HSP47 mRNA insert, which enabled us to perform the Northern hybridization analysis.


  1. 1.
    Lamy M, Fallat RJ, Koeniger E, et al. (1976) Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114:267–284PubMedGoogle Scholar
  2. 2.
    Collins JF, Smith JD, Coalson JJ, Johanson WG Jr (1984) Variability in lung collagen amounts after prolonged support of acute respiratory failure. Chest 85:641–646CrossRefPubMedGoogle Scholar
  3. 3.
    Raghu G, Striker LJ, Hudson LD, Striker GE (1985) Extracellular matrix in normal and fibrotic human lungs. Am Rev Respir Dis 131:281–289PubMedGoogle Scholar
  4. 4.
    Kazuhiro N (1998) Expression and function of heat shock protein 47: a collagen-specific molecular chaperone in the endoplasmic reticulum. Matrix Biol 16:379–389CrossRefGoogle Scholar
  5. 5.
    Saga S, Nagata K, Chen WT, Yamada KM (1987) pH-dependent function, purification, and intracellular location of a major collagen-binding glycoprotein. J Cell Biol 105:517–527CrossRefPubMedGoogle Scholar
  6. 6.
    Natsume T, Koide T, Yokota S, Hirayshi K, Nagata K (1994) Interaction between collagen-binding stress protein HSP47 and collagen. J Biol Chem 269:31224–31228PubMedGoogle Scholar
  7. 7.
    Nakai A, Satoh M, Hirayoshi K, Nagata K (1992) Involvement of the stress protein HSP 47 in procollagen processing in the endoplasmic reticulum. J Cell Biol 117:903–914CrossRefPubMedGoogle Scholar
  8. 8.
    Satoh M, Hirayoshi K, Yoshida S, Hosokawa N, Nagata K (1996) Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol 133:469–483CrossRefPubMedGoogle Scholar
  9. 9.
    Nakai A, Hirayoshi K, Saga S, Yamada KM, Nagata K (1989) The transformation-sensitive heat shock protein HSP47 binds specifically to feutin. Biochem Biophys Res Commum 169:259–264CrossRefGoogle Scholar
  10. 10.
    Ashcroft T, Simpson JM, Timbrell V (1988) Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467–470CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Steltzer H, Krafft P (1999) Improved outcome of ARDS patients: are we really performing better? Intensive Care Med 25:887–889CrossRefPubMedGoogle Scholar
  12. 12.
    Razzaque MS, Le VT, Taguchi T (2005) Heat shock protein 47 and renal fibrogenesis. Contrib Nephrol 148:57–69CrossRefPubMedGoogle Scholar
  13. 13.
    Brown KE, Broadhurst KA, Mathahs MM, Brunt EM, Schmidt WN (2005) Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver. Lab Invest 85:789–797CrossRefPubMedGoogle Scholar
  14. 14.
    Razzaque MS, Taguchi T (1999) The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histol Histopathol 14:1199–1212PubMedGoogle Scholar
  15. 15.
    Razzaque MS, Nazneen A, Taguchi T (1998) Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases. Mod Pathol 11:1183–1188PubMedGoogle Scholar
  16. 16.
    Nakai A, Hirayoshi K, Saga S, Yamada KM, Nagata K (1989) The transformation sensitive heat shock protein (HSP47) binds specifically to fetuin. Biochem Biophys Res Commun 164:259–264CrossRefPubMedGoogle Scholar
  17. 17.
    Satoh M, Hirayoshi K, Yokota S, Hosokawa N, Nagata K (1996) Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol 133:469–483CrossRefPubMedGoogle Scholar
  18. 18.
    Nagata K (2003) HSP47 as a collagen-specific molecular chaperone: function and expression in normal mouse development. Semin Cell Dev Biol 14:275–282CrossRefPubMedGoogle Scholar
  19. 19.
    Nagata K, Yamada M (1986) Phosphorylation and transformation sensitivity of major collagen binding protein of fibroblasts. J Biol Chem 261:7531-7536PubMedGoogle Scholar
  20. 20.
    Takechi H, Hirayoshi K, Nakai A, et al. (1992) Molecular cloning of a mouse 47-kDa heat-shock protein (HSP47), a collagen-binding stress protein, and its expression during the differentiation of F9 teratocarcinoma cells. Eur J Biochem 206:323–329CrossRefPubMedGoogle Scholar
  21. 21.
    Hickey AJ, Conway de Macario E, Macario AJ (2002) Transcription in the archaea: basal factors, regulation, and stress-gene expression. Crit Rev Biochem Mol Biol 37:537–599CrossRefPubMedGoogle Scholar
  22. 22.
    Hosokawa N, Takechi H, Yokota S, Hirayoshi K, Nagata K (1993) Structure of the gene encoding the mouse 47-kDa heat-shock protein (HSP47). Gene 126:187–193CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Satoshi Hagiwara
    • 1
  • Hideo Iwasaka
    • 1
  • Shigekiyo Matsumoto
    • 1
  • Takayuki Noguchi
    • 1
  • Hidekatsu Yoshioka
    • 2
  1. 1.Department of Brain and Nerve Science, AnesthesiologyOita University Faculty of MedicineYufu CityJapan
  2. 2.Department of Anatomy, Biology and Medicine, BiochemistryOita University Faculty of MedicineYufu CityJapan

Personalised recommendations