Calreticulin is a negative regulator of bronchial smooth muscle cell proliferation

Miglino, N. and Roth, M. and Lardinois, D. and Tamm, M. and Borger, P.. (2012) Calreticulin is a negative regulator of bronchial smooth muscle cell proliferation. Journal of allergy, Vol. 2012, 783290.

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Official URL: http://edoc.unibas.ch/dok/A6338170

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Background. Calreticulin controls the C/EBPalphap42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPA mRNA. We determined the effects of steroids and long-acting beta-agonists on the p42/p30 ratio and on calreticulin expression in primary human bronchial smooth muscle (BSM) cells. Methods. The effects of budesonide (10(-8) M) and formoterol (10(-8) M) were studied in BSM cells pre-treated with siRNA targeting calreticulin. The expression of C/EBPalpha and calreticulin was determined by immuno-blotting. Automated cell counts were performed to measure proliferation. Results. All tested BSM cell lines (n = 5) expressed C/EBPalpha and calreticulin. In the presence of 5% FBS, the p42/p30 ratio significantly decreased (n = 3, P > 0.05) and coincided with BSM cell proliferation. High levels of calreticulin were associated with a decreased p42/p30 isoform ratio. FBS induced the expression of calreticulin (n = 3, P > 0.05), which was further increased by formoterol. siRNA targeting calreticulin increased the p42/p30 ratio in non-stimulated BSM cells and significantly inhibited the proliferation of PDGF-BB-stimulated BSM cells (n = 5, P > 0.05). Neither budesonide nor formoterol restored the p42 isoform expression. Conclusions. Our data show calreticulin is a negative regulator of C/EBPalpha protein expression in BSM cells. Modulation of calreticulin levels may provide a novel target to reduce BSM remodeling.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Tamm, Michael and Roth-Chiarello, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:10 Apr 2015 09:13

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