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Am J Physiol Lung Cell Mol Physiol. 2017 Aug 1;313(2):L328-L338. doi: 10.1152/ajplung.00284.2016. Epub 2017 May 4.

A novel role for primary cilia in airway remodeling.

Author information

1
Matrix Biology Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
2
Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, and Pulmonary Injury and Repair Center, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
3
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia; and.
4
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
5
Matrix Biology Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; garantziotis@niehs.nih.gov.

Abstract

Primary cilia (PC) are solitary cellular organelles that play critical roles in development, homeostasis, and disease pathogenesis by modulating key signaling pathways such as Sonic Hedgehog and calcium flux. The antenna-like shape of PC enables them also to facilitate sensing of extracellular and mechanical stimuli into the cell, and a critical role for PC has been described for mesenchymal cells such as chondrocytes. However, nothing is known about the role of PC in airway smooth muscle cells (ASMCs) in the context of airway remodeling. We hypothesized that PC on ASMCs mediate cell contraction and are thus integral in the remodeling process. We found that PC are expressed on ASMCs in asthmatic lungs. Using pharmacological and genetic methods, we demonstrated that PC are necessary for ASMC contraction in a collagen gel three-dimensional model both in the absence of external stimulus and in response to the extracellular component hyaluronan. Mechanistically, we demonstrate that the effect of PC on ASMC contraction is, to a small extent, due to their effect on Sonic Hedgehog signaling and, to a larger extent, due to their effect on calcium influx and membrane depolarization. In conclusion, PC are necessary for the development of airway remodeling by mediating calcium flux and Sonic Hedgehog signaling.

KEYWORDS:

contraction; extracellular matrix; hyaluronan; lung; smooth muscle cells

PMID:
28473325
PMCID:
PMC5582939
DOI:
10.1152/ajplung.00284.2016
[Indexed for MEDLINE]
Free PMC Article

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