Altered expression of calreticulin during the development of fibrosis

Abstract

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‐β, 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.