Muscarinic receptor stimulation augments TGF-beta(1)-induced contractile protein expression by airway smooth muscle cells

作者：Oenema Tjitske A^*; Smit Marieke; Smedinga Lyanne; Racke Kurt; Halayko Andrew J; Meurs Herman; Gosens Reinoud

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2012, 303(7): L589-L597.

DOI：10.1152/ajplung.00400.2011

• acetylcholine
• airway remodeling
• sm-alpha-actin
• calponin
• glycogen synthase kinase-3 beta
• 4E-binding protein 1
• asthma
• chronic obstructive pulmonary disease
• receptor cross-talk

Oenema TA, Smit M, Smedinga L, Racke K, Halayko AJ, Meurs H, Gosens R. Muscarinic receptor stimulation augments TGF-beta(1)-induced contractile protein expression by airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 303: L589-L597, 2012. First published August 3, 2012; doi:10.1152/ajplung.00400.2011.-Acetylcholine (ACh) is the primary parasympathetic neurotransmitter in the airways. Recently, it was established that ACh, via muscarinic receptors, regulates airway remodeling in animal models of asthma and chronic obstructive pulmonary disease (COPD). The mechanisms involved are not well understood. Here, we investigated the functional interaction between muscarinic receptor stimulation and transforming growth factor (TGF)-beta(1) on the expression of contractile proteins in human airway smooth muscle (ASM) cells. ASM cells expressing functional muscarinic M-2 and M-3 receptors were stimulated with methacholine (MCh), TGF-beta(1), or their combination for up to 7 days. Western blot analysis revealed a strong induction of sm-alpha-actin and calponin by TGF-beta(1), which was increased by MCh in ASM cells. Immunocytochemistry confirmed these results and revealed that the presence of MCh augmented the formation of sm-alpha-actin stress fibers by TGF-beta(1). MCh did not augment TGF-beta(1)-induced gene transcription of contractile phenotype markers. Rather, translational processes were involved in the augmentation of TGF-beta(1)-induced contractile protein expression by muscarinic receptor stimulation, including phosphorylation of glycogen synthase kinase-3 beta and 4E-binding protein 1, which was enhanced by MCh. In conclusion, muscarinic receptor stimulation augments functional effects of TGF-beta(1) in human ASM cells on cellular processes that underpin ASM remodeling in asthma and COPD.

• 出版日期2012-10