Lack of fibulin-3 alters regenerative tissue responses in the primary olfactory pathway

Jana Vukovic, Lihua Y. Marmorstein, Precious J. McLaughlin, Takako Sasaki, Giles W. Plant, Alan R. Harvey, Marc J. Ruitenberg

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The adult olfactory epithelium has maintained the ability to reconstitute its olfactory sensory neurons (OSNs) from a basal progenitor cell compartment. This allows for life-long turnover and replacement of receptor components as well as repair of the primary olfactory pathway in response to injury and environmental insults. The present study investigated whether fibulin-3, a glycoprotein in the extracellular matrix and binding partner of tissue inhibitor of metalloproteinases-3 (TIMP-3), plays a role in ongoing plasticity and regenerative events in the adult primary olfactory pathway. In wild-type control mice, fibulin-3 protein was detected on IB4+CD31+ blood vessels, nerve fascicles and the basement membrane underneath the olfactory epithelium. After target ablation (olfactory bulbectomy), fibulin-3 was also abundantly present in the central nervous system (CNS) scar tissue that occupied the bulbar cavity. Using two different lesion models, i.e. intranasal Triton X-100 lesion and olfactory bulbectomy, we show that fibulin-3 deficient (Efemp1-/-) mice have impaired recovery of the olfactory epithelium after injury. Ten days post-injury, Efemp1-/- mice showed altered basal stem/progenitor cell proliferation and increased overall numbers of mature (olfactory marker protein (OMP) -positive) versus immature OSNs. However, compromised regenerative capacity of the primary olfactory pathway in Efemp1-/- mice was evidenced by reduced numbers of mature OSNs at the later time point of 42 days post-injury. In addition to these neural differences there were consistent changes in blood vessel structure in the olfactory lamina propria of Efemp1-/- mice. Overall, these data suggest a role for fibulin-3 in tissue maintenance and regeneration in the adult olfactory pathway.

Original languageEnglish (US)
Pages (from-to)406-415
Number of pages10
JournalMatrix Biology
Volume28
Issue number7
DOIs
StatePublished - Sep 1 2009

Keywords

  • FBLN
  • Neural scar
  • Olfactory ensheathing cells
  • PECAM-1
  • Peripheral nervous system
  • Vasculature

ASJC Scopus subject areas

  • Molecular Biology

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    Vukovic, J., Marmorstein, L. Y., McLaughlin, P. J., Sasaki, T., Plant, G. W., Harvey, A. R., & Ruitenberg, M. J. (2009). Lack of fibulin-3 alters regenerative tissue responses in the primary olfactory pathway. Matrix Biology, 28(7), 406-415. https://doi.org/10.1016/j.matbio.2009.06.001