Altered expression of calreticulin during the development of fibrosis.
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.
Department of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Katerina P
KP
Kypreou
Panagiotis
P
Kavvadas
Panagiotis
P
Karamessinis
Michalis
M
Peroulis
Avra
A
Alberti
Paschalis
P
Sideras
Stelios
S
Psarras
Yasemie
Y
Capetanaki
Panagiotis K
PK
Politis
Aristidis S
AS
Charonis
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D003893:Desmin / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D040901:Proteomics / Q000379:methods; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D037282:Calreticulin; D003893:Desmin; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D003094:Collagen