TNF-α-converting enzyme/A disintegrin and metalloprotease - 17 mediates mechanotransduction in murine tracheal epithelial cells

Tetsuya Shiomi, Daniel J. Tschumperlin, Jin Ah Park, Susan W. Sunnarborg, Keisuke Horiuchi, Carl P. Blobel, Jeffrey M. Drazen

研究成果: Article

16 引用 (Scopus)

抄録

Bronchoconstriction applies compressive stress to airway epithelial cells. We show that the application of compressive stress to cultured murine tracheal epithelial cells elicits the increased phosphorylation of extracellular signal-regulated kinase (ERK) and Akt through an epidermal growth factor receptor (EGFR)-dependent process, consistent with previous observations of the bronchoconstrictioninduced activation of EGFR in both human and murine airways. Mechanotransduction requires metalloprotease activity, indicating a pivotal role for proteolytic EGF-family ligand shedding. However, cells derived from mice with targeted deletions of the EGFR ligands Tgfα and Hb-egf showed only modest decreases in responses, even when combined with neutralizing antibodies to the EGFR ligands epiregulin and amphiregulin, suggesting redundant or compensatory roles for individual EGF family members in mechanotransduction. In contrast, cells harvested from mice with a conditional deletion of the gene encoding the TNF-α-converting enzyme (TACE/ADAM17), a sheddase for multiple EGF-family proligands, displayed a near-complete attenuation of ERK and Akt phosphorylation responses and compressive stress-induced gene regulation. Our data provide strong evidence that TACE plays a critical central role in the transduction of compressive stress.

元の言語English
ページ(範囲)376-385
ページ数10
ジャーナルAmerican Journal of Respiratory Cell and Molecular Biology
45
発行部数2
DOI
出版物ステータスPublished - 2011 8 1

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Disintegrins
Metalloproteases
Compressive stress
Epidermal Growth Factor Receptor
Epithelial Cells
Epidermal Growth Factor
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Enzymes
Ligands
Gene encoding
Bronchoconstriction
Gene Deletion
Neutralizing Antibodies
Gene expression
Chemical activation
Genes
ADAM17 Protein

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

これを引用

TNF-α-converting enzyme/A disintegrin and metalloprotease - 17 mediates mechanotransduction in murine tracheal epithelial cells. / Shiomi, Tetsuya; Tschumperlin, Daniel J.; Park, Jin Ah; Sunnarborg, Susan W.; Horiuchi, Keisuke; Blobel, Carl P.; Drazen, Jeffrey M.

:: American Journal of Respiratory Cell and Molecular Biology, 巻 45, 番号 2, 01.08.2011, p. 376-385.

研究成果: Article

Shiomi, Tetsuya ; Tschumperlin, Daniel J. ; Park, Jin Ah ; Sunnarborg, Susan W. ; Horiuchi, Keisuke ; Blobel, Carl P. ; Drazen, Jeffrey M. / TNF-α-converting enzyme/A disintegrin and metalloprotease - 17 mediates mechanotransduction in murine tracheal epithelial cells. :: American Journal of Respiratory Cell and Molecular Biology. 2011 ; 巻 45, 番号 2. pp. 376-385.
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