Novel non-canonical TGF-β signaling networks: Emerging roles in airway smooth muscle phenotype and function - 02/02/13

Doi : 10.1016/j.pupt.2012.07.006

Behzad Yeganeh ^a,^b, Subhendu Mukherjee ^g, Lyn M. Moir ^e,^f, Kuldeep Kumawat ^c, Hessam H. Kashani ^a,^b, Rushita A. Bagchi ^d, Hoeke A. Baarsma ^c, Reinoud Gosens ^c, Saeid Ghavami ^a,^b,^⁎
^a Department of Physiology, Manitoba Institute of Child Health, University of Manitoba, 675 McDermot Ave, Winnipeg, Canada
^b Biology of Breathing Theme, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Canada
^c Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
^d Department of Physiology, St. Boniface Research Centre, University of Manitoba, Winnipeg, Canada
^e Cell Biology Group, Woolcock Institute of Medical Research, Glebe, NSW 2050, Australia
^f Discipline of Pharmacology, The University of Sydney, NSW 2006, Australia
^g Firestone Institute for Respiratory Health, St. Joseph’s Hospital, Departments of Medicine, McMaster University, Hamilton, Ontario, Canada

Corresponding author. Department of Physiology, Manitoba Institute of Child Health, University of Manitoba, 675 McDermot Ave, Winnipeg, Canada. Tel.: +1 204 480 1327; fax: +1 204 789 4915.

Abstract

The airway smooth muscle (ASM) plays an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). ASM cells express a wide range of receptors involved in contraction, growth, matrix protein production and the secretion of cytokines and chemokines. Transforming growth factor beta (TGF-β) is one of the major players in determining the structural and functional abnormalities of the ASM in asthma and COPD. It is increasingly evident that TGF-β functions as a master switch, controlling a network of intracellular and autocrine signaling loops that effect ASM phenotype and function. In this review, the various elements that participate in non-canonical TGF-β signaling, including MAPK, PI3K, WNT/β-catenin, and Ca²⁺, are discussed, focusing on their effect on ASM phenotype and function. In addition, new aspects of ASM biology and their possible association with non-canonical TGF-β signaling will be discussed.

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Keywords : Asthma, Chronic obstructive pulmonary disease, WNT/β-catenin signaling, PI3K signaling, Calcium, Autophagy, S100 proteins, HMGB1

Plan

Introduction

The role of TGF-β in asthma and COPD

TGF-β and the PI3K signaling pathway

TGF-β and WNT signaling

TGF-β and calcium signaling

Cross-talk between DAMPs and TGF-β and their role in asthma and COPD

TGF-β and autophagy, possible function in asthma and COPD pathophysiology

Scleraxis and TGF-β: possible role of scleraxis in ECM synthesis by ASM

Future directions and conclusions

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Vol 26 - N° 1

P. 50-63 - février 2013 Retour au numéro

Article précédent

Phenotype modulation of airway smooth muscle in asthma
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Pro-inflammatory and immunomodulatory functions of airway smooth muscle: Emerging concepts
Yuxiu C. Xia, Naresh Singh Redhu, Lyn M. Moir, Cynthia Koziol-White, Alaina J. Ammit, Laila Al-Alwan, Blanca Camoretti-Mercado, Rachel L. Clifford

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Novel non-canonical TGF-β signaling networks: Emerging roles in airway smooth muscle phenotype and function - 02/02/13

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