Abstract
Aim:
To determine whether protein kinase C (PKC) has any effect on the expression of cyclinD1, a key regulator of growth control and G1/S transition, and to investigate the underlying molecular mechanisms of PKC involving the remodeling of the asthmatic airway smooth muscle (ASM).
Methods:
The treatment of synchronized ASM cells from asthmatic rats with PKC-specific agonist phorbol 12-myristate 13-acetate (PMA) and antagonist 2-{1-[3-(amidinothio) propyl]-1H-indol-3-yl}-3-(1-methylindol-3-yl) maleimide methanesulfonate salt (Ro31-8220) was followed by the proliferation assay. PKCα and cyclinD1 expressions in ASM cells (ASMC) were detected by RT-PCR and Western blotting. The relation between PKCα and cyclinD1 was assessed by linear regression analysis. The effect of the construct recombinant plasmid pcDNA3.1-antisense cyclinD1 (pcDNA3.1-ascyclinD1) on the proliferation of ASMC was found to be induced by PMA.
Results:
The data showed phorbol ester-dependent PKCα promoted the proliferation of ASMC. The closely-positive correlation existed between the expression of PKCα and cyclinD1 at the transcriptional (r=0.821, P<0.01) and transla-tional (r=0.940, P<0.01) levels. pcDNA3.1-ascyclinD1 could inhibit the proliferation of ASMC. pcDNA3.1-ascyclinD1 almost completely attenuated the PMA-induced proliferation effect as Ro31-8220+pcDNA3.1.
Conclusion:
The proliferation of ASMC by PKC might by regulated by the cyclinD1 expression in asthmatic rats.
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This work was supported by the National Natural Science Foundation of China (No 3067092).
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Qiao, Lf., Xu, Yj., Liu, Xs. et al. PKC promotes proliferation of airway smooth muscle cells by regulating cyclinD1 expression in asthmatic rats. Acta Pharmacol Sin 29, 677–686 (2008). https://doi.org/10.1111/j.1745-7254.2008.00795.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00795.x
