Induction of an epithelial integrin αVβ6 in human cytomegalovirus-infected endothelial cells leads to activation of transforming growth factor-β1 and increased collagen production

Takako Tabata, Hisaaki Kawakatsu, Ekaterina Maidji, Takao Sakai, Keiko Sakai, June Fang-Hoover, Motohiko Aiba, Dean Sheppard, Lenore Pereira

研究成果: ジャーナルへの寄稿学術論文査読

40 被引用数 (Scopus)

抄録

Human cytomegalovirus (CMV) infection is a major cause of morbidity in immunosuppressed individuals, and congenital CMV infection is a leading cause of birth defects in newborns. Infection with pathogenic viral strains alters cell-cell and cell-matrix interactions, affecting extracellular matrix remodeling and endothelial cell migration. The multifunctional cytokine transforming growth factor (TGF)-β1 regulates cell proliferation, differentiation, and extracellular matrix remodeling. Secreted as a latent protein complex, TGF-β1 requires activation before binding to receptors that phosphorylate intracellular effectors. TGF-β1 is activated by integrin αvβ6, which is strongly induced in the epithelium by injury and inflammation but has not previously been found in endothelial cells. Here, we report that CMV infection induces integrin αvβ6 expression in endothelial cells , leading to activation of TGF-β1, signaling through its receptor ALK5, and phosphorylation of its intracellular effector Smad3. Infection of endothelial cells was also found to stimulate collagen synthesis through a mechanism dependent on both TGF-β1 and integrin αvβ6. Immunohistochemical analysis showed integrin αvβ6 up-regulation in capillaries proximal to foci of CMV infection in lungs, salivary glands, uterine decidua, and injured chorionic villi of the placenta, demonstrating both its induction in endothelium and upregulation in epithelium in vivo. Our results suggest that activation of TGF-β1 by integrin αvβ6 contributes to pathological changes and may impair endothelial cell functions in tissues that are chronically infected with CMV.

本文言語英語
ページ(範囲)1127-1140
ページ数14
ジャーナルAmerican Journal of Pathology
172
4
DOI
出版ステータス出版済み - 04-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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