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査読

20 被引用数 (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.

本文言語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
2
DOI
出版ステータスPublished - 2011 8 1
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

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