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Publication Detail

Title: A novel role for primary cilia in airway remodeling.

Authors: Trempus, Carol S; Song, Weifeng; Lazrak, Ahmed; Yu, Zhihong; Creighton, Judy R; Young, Bethany M; Heise, Rebecca L; Yu, Yen Rei; Ingram, Jennifer L; Tighe, Robert M; Matalon, Sadis; Garantziotis, Stavros

Published In Am J Physiol Lung Cell Mol Physiol, (2017 08 01)

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.

PubMed ID: 28473325 Exiting the NIEHS site

MeSH Terms: Airway Remodeling/physiology*; Asthma/metabolism; Asthma/pathology; Bronchi/metabolism; Bronchi/pathology*; Cell Membrane/metabolism; Cell Membrane/pathology; Cells, Cultured; Cilia/metabolism; Cilia/pathology*; HEK293 Cells; Hedgehog Proteins/metabolism; Humans; Membrane Potentials/physiology; Myocytes, Smooth Muscle/metabolism; Myocytes, Smooth Muscle/pathology; Signal Transduction/physiology

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