Document Detail

Mechanical stretch induces epithelial-mesenchymal transition in alveolar epithelia via hyaluronan activation of innate immunity.
MedLine Citation:
PMID:  21398522     Owner:  NLM     Status:  MEDLINE    
Epithelial injury is a central event in the pathogenesis of many inflammatory and fibrotic lung diseases like acute respiratory distress syndrome, pulmonary fibrosis, and iatrogenic lung injury. Mechanical stress is an often underappreciated contributor to lung epithelial injury. Following injury, differentiated epithelia can assume a myofibroblast phenotype in a process termed epithelial to mesenchymal transition (EMT), which contributes to aberrant wound healing and fibrosis. We demonstrate that cyclic mechanical stretch induces EMT in alveolar type II epithelial cells, associated with increased expression of low molecular mass hyaluronan (sHA). We show that sHA is sufficient for induction of EMT in statically cultured alveolar type II epithelial cells and necessary for EMT during cell stretch. Furthermore, stretch-induced EMT requires the innate immune adaptor molecule MyD88. We examined the Wnt/β-catenin pathway, which is known to mediate EMT. The Wnt target gene Wnt-inducible signaling protein 1 (wisp-1) is significantly up-regulated in stretched cells in hyaluronan- and MyD88-dependent fashion, and blockade of WISP-1 prevents EMT in stretched cells. In conclusion, we show for the first time that innate immunity transduces mechanical stress responses through the matrix component hyaluronan, and activation of the Wnt/β-catenin pathway.
Rebecca L Heise; Vandy Stober; Chaitra Cheluvaraju; John W Hollingsworth; Stavros Garantziotis
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-03-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-16     Completed Date:  2011-07-26     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17435-44     Citation Subset:  IM    
Copyright Information:
© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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MeSH Terms
CCN Intercellular Signaling Proteins
Epithelial-Mesenchymal Transition / drug effects,  physiology*
Hyaluronic Acid / immunology,  metabolism,  pharmacology*
Immunity, Innate / drug effects,  physiology*
Mice, Knockout
Myeloid Differentiation Factor 88 / genetics,  immunology,  metabolism
Oncogene Proteins / genetics,  immunology,  metabolism
Proto-Oncogene Proteins
Pulmonary Alveoli / cytology,  immunology,  metabolism*
Respiratory Mucosa / cytology,  metabolism*
Stress, Physiological / drug effects,  physiology*
Wnt Proteins / genetics,  immunology,  metabolism
beta Catenin / genetics,  immunology,  metabolism
Grant Support
Reg. No./Substance:
0/CCN Intercellular Signaling Proteins; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Oncogene Proteins; 0/Proto-Oncogene Proteins; 0/Wisp1 protein, mouse; 0/Wnt Proteins; 0/beta Catenin; 9004-61-9/Hyaluronic Acid

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