Document Detail

PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration.
MedLine Citation:
PMID:  22037358     Owner:  NLM     Status:  MEDLINE    
The phosphoinositide-3 kinase/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased wound repair during PTEN inhibition are not yet well established. Using primary human lung epithelia and a related lung epithelial cell line, we first determined whether changes in migration or proliferation account for wound closure. Strikingly, we observed that cell migration accounts for the majority of wound recovery following PTEN inhibition in conjunction with activation of the Akt and ERK signaling pathways. We then used fluorescence and atomic force microscopy to investigate how PTEN inhibition alters the cytoskeletal and mechanical properties of the epithelial cell. PTEN inhibition did not significantly alter cytoskeletal structure but did result in large spatial variations in cell stiffness and in particular a decrease in cell stiffness near the wound edge. Biomechanical changes, as well as migration rates, were mediated by both the Akt and ERK pathways. Our results indicate that PTEN inhibition rapidly alters biochemical signaling events that in turn provoke alterations in biomechanical properties that enhance cell migration. Specifically, the reduced stiffness of PTEN-inhibited cells promotes larger deformations, resulting in a more migratory phenotype. We therefore conclude that increased wound closure consequent to PTEN inhibition occurs through enhancement of cell migration that is due to specific changes in the biomechanical properties of the cell.
Cosmin Mihai; Shengying Bao; Ju-Ping Lai; Samir N Ghadiali; Daren L Knoell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-28
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  302     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-03     Completed Date:  2012-03-22     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L287-99     Citation Subset:  IM    
Department of Biomedical Engineering, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
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MeSH Terms
Actin Cytoskeleton / metabolism
Cell Line
Cell Movement / drug effects*
Cell Proliferation
Electric Impedance
Epithelial Cells / drug effects,  metabolism,  physiology*
Extracellular Signal-Regulated MAP Kinases / metabolism
Lung / cytology*
Lung Injury / drug therapy,  prevention & control
MAP Kinase Signaling System
Microscopy, Atomic Force
PTEN Phosphohydrolase / antagonists & inhibitors*,  metabolism
Proto-Oncogene Proteins c-akt / metabolism
Vanadium Compounds / pharmacology*
Wound Healing / drug effects*
Grant Support
R01 HL086981-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Vanadium Compounds; 0/bisperoxovanadium; EC Proteins c-akt; EC Signal-Regulated MAP Kinases; EC protein, human; EC Phosphohydrolase

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