ERM is expressed by alveolar epithelial cells in adult mouse lung and regulates caveolin-1 transcription in mouse lung epithelial cell lines

2007 ◽  
Vol 102 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Hasmeena Kathuria ◽  
YuXia Cao ◽  
Anne Hinds ◽  
Maria I. Ramirez ◽  
Mary C. Williams
2014 ◽  
Vol 306 (8) ◽  
pp. L786-L796 ◽  
Author(s):  
Jibing Yang ◽  
Miranda Velikoff ◽  
Ernesto Canalis ◽  
Jeffrey C. Horowitz ◽  
Kevin K. Kim

Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.


Toxicology ◽  
1997 ◽  
Vol 123 (1-2) ◽  
pp. 53-100 ◽  
Author(s):  
Alvin M Malkinson ◽  
Lori D Dwyer-Nield ◽  
Pamela L Rice ◽  
David Dinsdale

2008 ◽  
Vol 76 (7) ◽  
pp. 2833-2842 ◽  
Author(s):  
Robin R. Craven ◽  
Joshua D. Hall ◽  
James R. Fuller ◽  
Sharon Taft-Benz ◽  
Thomas H. Kawula

ABSTRACT Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, causes disseminating infections in humans and other mammalian hosts. Macrophages and other monocytes have long been considered the primary site of F. tularensis replication in infected animals. However, recently it was reported that F. tularensis also invades and replicates within alveolar epithelial cells following inhalation in a mouse model of tularemia. TC-1 cells, a mouse lung epithelial cell line, were used to study the process of F. tularensis invasion and intracellular trafficking within nonphagocytic cells. Live and paraformaldehyde-fixed F. tularensis live vaccine strain organisms associated with, and were internalized by, TC-1 cells at similar frequencies and with indistinguishable differences in kinetics. Inhibitors of microfilament and microtubule activity resulted in significantly decreased F. tularensis invasion, as did inhibitors of phosphatidylinositol 3-kinase and tyrosine kinase activity. Collectively, these results suggest that F. tularensis epithelial cell invasion is mediated by a preformed ligand on the bacterial surface and driven entirely by host cell processes. Once internalized, F. tularensis-containing endosomes associated with early endosome antigen 1 (EEA1) followed by lysosome-associated membrane protein 1 (LAMP-1), with peak coassociation frequencies occurring at 30 and 120 min postinoculation, respectively. By 2 h postinoculation, 70.0% (± 5.5%) of intracellular bacteria were accessible to antibody delivered to the cytoplasm, indicating vacuolar breakdown and escape into the cytoplasm.


2001 ◽  
Vol 27 (3) ◽  
pp. 297-318 ◽  
Author(s):  
Amy L. McDoniels-Silvers ◽  
Christopher R. Herzog ◽  
Frederick L. Tyson ◽  
Alvin M. Malkinson ◽  
Ming You

2005 ◽  
Vol 26 (7) ◽  
pp. 1196-1206 ◽  
Author(s):  
Lori D. Dwyer-Nield ◽  
Mary C. Srebernak ◽  
Bradley S. Barrett ◽  
Jinhee Ahn ◽  
Pippa Cosper ◽  
...  

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