Altered expression of calreticulin during the development of fibrosis |
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Authors: | Kypreou Katerina P Kavvadas Panagiotis Karamessinis Panagiotis Peroulis Michalis Alberti Avra Sideras Paschalis Psarras Stelios Capetanaki Yasemie Politis Panagiotis K Charonis Aristidis S |
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Institution: | Department of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. |
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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-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. |
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Keywords: | Calreticulin Epithelial to mesenchymal transition Fibrosis TGF‐b1 |
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