Differences in gene expression profiles from asbestos-treated SPARC-null and wild-type mouse lungs

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Abstract

The role of SPARC in the in vivo lung response to crocidolite asbestos was addressed by instillation of crocidolite asbestos in a series of wild-type or SPARC-null mice. Animals were sacrificed at one week, one month, and three months post-instillation to assess the impact of SPARC on multiple stages in the development of fibrosis. RNA was harvested from 10 animals/time point, pooled, and used to probe a mouse array containing ∼ 10,000 probes. Gene expression data were analyzed for fold change, and for broader functional group alterations. As expected, the one-week time point displayed alterations in genes involved in immune recognition, energy utilization, and growth factor production. Later time points showed expression alterations for genes involved in protein degradation, Wnt receptor signaling, membrane protein activity, and transport. Molecules in the Wnt pathway have been implicated in bone growth, mediation of fibroblast activity, and have been directly linked to SPARC regulation.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalGenomics
Volume94
Issue number2
DOIs
StatePublished - Aug 2009

Funding

The authors acknowledge E. Helene Sage (Bennaroya Research Institute at Virginia Mason) for the kind gift of the SPARC-null mice. Support towards the publication of this manuscript came from the Montana NSF EPSCoR grant: EPS-03464558 and the State of Montana MBRCT grant: Agreement #07-04 (2004-2007) (MP and EAP); and the CDC through a subproject under grant number CCR822092 (EP). This publication was also made possible by both subproject (MP and EAP) and core facility (MP) support from Grant Number P20RR017670 and core facility support (MP) from Grant Number P20RR015583, both from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The views expressed in this publication do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

FundersFunder number
Centers for Disease Control and PreventionCCR822092
R21ES011676
P20RR015583, P20RR017670
07-04 (2004-2007, EPS-03464558

    Keywords

    • Amphibole
    • Asbestos
    • Fibrosis
    • Hevin
    • Knockout mice
    • Microarray analysis
    • Osteonectin
    • SPARC

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