Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions

Eytan Wine, Grace Shen-Tu, Melanie Gareau, Harvey A. Goldberg, Christoph Licht, Bo Yee Ngan, Esben S. Sorensen, James Greenaway, Jaro Sodek, Ron Zohar, Philip M. Sherman

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN-/- fibroblasts were incubated with C. rodentium and attachingeffacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN-/- mice, and spleen enlargement by infection was absent in OPN-/- mice. Rectal administration of OPN to OPN -/- mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN-/- mice, compared with wild-type mice, which was accompanied by reduced attaching - effacing lesions, both in infected OPN-/- mice and OPN-/- mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN-/- cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

Original languageEnglish (US)
Pages (from-to)1320-1332
Number of pages13
JournalAmerican Journal of Pathology
Volume177
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Wine, E., Shen-Tu, G., Gareau, M., Goldberg, H. A., Licht, C., Ngan, B. Y., Sorensen, E. S., Greenaway, J., Sodek, J., Zohar, R., & Sherman, P. M. (2010). Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions. American Journal of Pathology, 177(3), 1320-1332. https://doi.org/10.2353/ajpath.2010.091068