title: A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University, Providence, Rhode Island 02905, USA.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Maciejewski
authors.forename: Diana
authors.initials: D
authors.lastname: Drouillard
authors.forename: Melissa
authors.initials: M
authors.lastname: Santos
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hokenson
authors.forename: Renda L
authors.initials: RL
authors.lastname: Hawwa
authors.forename: Zheping
authors.initials: Z
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Esteban
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D003505:Cyclodextrins / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D008168:Lung / Q000196:embryology*; D040542:Mechanotransduction, Cellular; D021962:Membrane Microdomains / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
chemical_list: D051242:Caveolin 1; D003505:Cyclodextrins; D037721:Pulmonary Surfactant-Associated Protein C; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases