Functional role of caveolin-1 in airway smooth muscle cells proliferation and regulatory effect of roxithromycin

Abstract

To explore the functional role of caveolin-1 in airway smooth muscle cells (ASMCs) proliferation and examine the regulatory effect of roxithromycin. The rat model of bronchial asthma was established. Electron microscope was employed to observe the status of caveolae and light microscope for the histological changes in pulmonary tissues. The primarily cultured ASMCs were divided into 5 groups: control (group A), asthmatic ASMCs (group B), PD98059 (group C), roxithromycin (group D) and methyl-β-cyclodextrin (group E). Cell proliferation was detected by Cell Counting Kit-8 (CCK-8). And the expressions of caveolin-1, extracellular regulated protein kinases (ERK) and monocyte chemotactic protein (MCP)-1 were detected by Western blot and reverse transcription polymerase chain reaction (RT-PCR). The cell proliferation of asthmatic ASMCs (0.68 ± 0.15, 0.63 ± 0.13) in groups C and D were significantly less than those in group B (0.96 ± 0.14) (both P < 0.05) while group E was more than group B (1.26 ± 0.11 vs 0.96 ± 0.14, P < 0.05). The content of caveolin-1 (0.392 ± 0.064, 0.332 ± 0.057) in groups C and D were higher than those in group B (0.237 ± 0.032) (both P < 0.05) while ERK1/2 protein level in groups C and D (0.241 ± 0.017, 0.268 ± 0.007) were less than those in group B (0.346 ± 0.009) (both P < 0.01). And MCP-1 protein level in groups C and D (0.198 ± 0.015, 0.286 ± 0.019) were less than those in group B (0.482 ± 0.026) (both P < 0.01). The ERK mRNA level in groups C and D (0.277 ± 0.043, 0.338 ± 0.026) were less than those in group B (0.591 ± 0.022) (both P < 0.01). And also MCP-1 mRNA in groups C and D (0.212 ± 0.042, 0.249 ± 0.032) were less than those in group B (0.676 ± 0.053) (all P < 0.01) CONCLUSIONS: Caveolin-1 preventing the proliferation of asthmatic ASMCs is most likely mediated by ERK1/2 signal pathway and a down-regulation of MCP-1 expression. And roxithromycin reduces the proliferation of asthmatic ASMCs through up-regulating the expression of caveolin-1 and inhibiting the expression of MCP-1.