Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.

Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.

Gombedza Farai; Kondeti Vinay; Al-Azzam Nosayba; Koppes Stephanie; Duah Ernest; Patil Prachi; Hexter Madison; Phillips Daniel; Thodeti Charles K; Paruchuri Sailaja

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2017

2017-04

Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4-knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4-knockout mice showed diminished differentiation potential compared with wild-type mice. Fibroblasts from asthmatic lung exhibited increased TRPV4 activity and enhanced differentiation potential compared with normal human lung fibroblasts. Of interest, TGF-beta1 treatment enhanced TRPV4 activation in a

*Airway Remodeling; *fibronectin; *myofibroblasts; *PAI-1; *PI3K; *TGF-beta1; Adult; Animals; Asthma/etiology/genetics/*metabolism/pathology; Cells; Cultured; Dermatophagoides farinae/immunology; Extracellular Matrix/*metabolism/pathology; Fibroblasts/metabolism; Fibronectins/*metabolism; Humans; Inbred C57BL; Male; Mice; Phosphatidylinositol 3-Kinases/metabolism; Plasminogen Activator Inhibitor 1/metabolism; Transforming Growth Factor beta/metabolism; TRPV Cation Channels/genetics/*metabolism

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1556–1570

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