Altered expression of calreticulin during the development of fibrosis

Proteomics. 2008 Jun;8(12):2407-19. doi: 10.1002/pmic.200700831.


Tissue damage following injury leads to inflammation and fibrosis. To understand the molecular mechanisms and the proteins involved in the fibrotic process, we used the well-established unilateral ureteric obstruction rat model and we analyzed the alterations at early and late time intervals using a classical proteomic approach. Data analysis demonstrates a correlation between calreticulin up-regulation and progression of fibrosis. Calreticulin is involved in Ca++ homeostasis but has not been previously implicated in animal models of fibrosis. Proteomic analysis consistently revealed up-regulation of calreticulin in both early and late time intervals. These findings were further confirmed by biochemical and morphological approaches. Next, animal models of lung fibrosis (bleomycin-induced) and heart fibrosis (desmin-null) were examined. In the lung model, calreticulin expression was up-regulated from early time intervals, whereas in the heart model no change in the expression of calreticulin was observed. In addition, TGF-beta, a well known major contributing factor in several fibrotic processes, was found to up-regulate calreticulin in cultured human proximal tubule epithelial cells. The above observations suggest that calreticulin might be involved in fibrotic processes; however the mechanism(s) underlying its possible involvement are yet unresolved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / toxicity
  • Calreticulin / genetics
  • Calreticulin / metabolism*
  • Cell Line, Transformed
  • Cells, Cultured
  • Collagen / biosynthesis
  • Desmin / genetics
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fibrosis / genetics*
  • Fibrosis / metabolism*
  • Gene Expression Regulation* / drug effects
  • Gene Expression Regulation* / physiology
  • Humans
  • Immunohistochemistry
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Biological
  • Proteomics / methods
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology


  • Calreticulin
  • Desmin
  • Transforming Growth Factor beta
  • Bleomycin
  • Collagen