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A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells.

Authors: Wang, Y  Maciejewski, BS  Drouillard, D  Santos, M  Hokenson, MA  Hawwa, RL  Huang, Z  Sanchez-Esteban, J 
Citation: Wang Y, etal., Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L775-83. Epub 2010 Feb 19.
Pubmed: (View Article at PubMed) PMID:20172952
DOI: Full-text: DOI:10.1152/ajplung.00327.2009

Mechanical forces are critical for fetal lung development. Using surfactant protein C (SP-C) as a marker, we previously showed that stretch-induced fetal type II cell differentiation is mediated via the ERK pathway. Caveolin-1, a major component of the plasma membrane microdomains, is important as a signaling protein in blood vessels exposed to shear stress. Its potential role in mechanotransduction during fetal lung development is unknown. Caveolin-1 is a marker of type I epithelial cell phenotype. In this study, using immunocytochemistry, Western blotting, and immunogold electron microscopy, we first demonstrated the presence of caveolin-1 in embryonic day 19 (E19) rat fetal type II epithelial cells. By detergent-free purification of lipid raft-rich membrane fractions and fluorescence immunocytochemistry, we found that mechanical stretch translocates caveolin-1 from the plasma membrane to the cytoplasm. Disruption of the lipid rafts with cholesterol-chelating agents further increased stretch-induced ERK activation and SP-C gene expression compared with stretch samples without disruptors. Similar results were obtained when caveolin-1 gene was knocked down by small interference RNA. In contrast, adenovirus overexpression of the wild-type caveolin-1 or delivery of caveolin-1 scaffolding domain peptide inside the cells decreased stretch-induced ERK phosphorylation and SP-C mRNA expression. In conclusion, our data suggest that caveolin-1 is present in E19 fetal type II epithelial cells. Caveolin-1 is translocated from the plasma membrane to the cytoplasm by mechanical stretch and functions as an inhibitory protein in stretch-induced type II cell differentiation via the ERK pathway.

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CRRD Object Information
CRRD ID: 6849300
Created: 2012-08-02
Species: All species
Last Modified: 2012-08-02
Status: ACTIVE



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