Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.
*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
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
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
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1096/fj.201601045R" target="_blank" rel="noreferrer noopener">10.1096/fj.201601045R</a>
Pertubation of beta1 integrin function using anti-sense or function-blocking antibodies on corneal cells grown on fibronectin and tenascin.
Animals; Antisense/*pharmacology; Cattle; Cell Adhesion; Cell Culture Techniques/*methods; Cells; Chick Embryo; Chickens; Complementary/metabolism; Cornea/*cytology; Cultured; DNA; Dose-Response Relationship; Drug; Fibronectins/*metabolism; Fluorescence; Immunohistochemistry; Integrin beta1/*metabolism/*physiology; Integrins/metabolism; Microscopy; Oligonucleotides; Protein Binding; Retroviridae/genetics; Tenascin/*metabolism
During corneal development, neural crest derivatives from the periocular mesenchyme migrate into the cornea and differentiate into corneal fibroblasts. During this time, these cells interact with a variety of extracellular matrices for proper orientation and development. In the present studies, we have examined the interaction of beta(1) integrins on periocular mesenchyme cells (POM) and corneal fibroblasts (CF) with fibronectin and tenascin by perturbing the function of this integrin. POM and CF attached and spread to a much greater extent on fibronectin than on tenascin. An antibody against beta(1) integrin, CSAT, decreased spreading and attachment, and resulted in a lack of immuno-detectable beta(1) integrin in focal adhesions on fibronectin; few beta(1) positive focal adhesions were observed in cells grown on tenascin. An anti-sense retroviral construct decreased endogenous levels of beta(1) integrin protein, and caused decreased attachment and spreading as well as sparse, disorganized focal adhesions. These data indicate that in vitro, both POM and CF have beta(1) integrins that interact with fibronectin and allow them to attach and spread, while tenascin is anti-adhesive. Further studies using both of these experimental paradigms will clarify whether these interactions also occur in vivo.
Doane Kathleen J; Bhattacharya Raka; Marchant Jeff
Cell biology international
2002
1905-6
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/cbir.2001.0818" target="_blank" rel="noreferrer noopener">10.1006/cbir.2001.0818</a>