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

Our plain-English summary of Differences in gene expression profiles from asbestos-treated SPARC-null and wild-type mouse lungs, by M.A. Pershouse, A.M. Smartt, C. Schwanke, et al (Genomics, 2009).

The study

• Authors: M.A. Pershouse, A.M. Smartt, C. Schwanke, E.A. Putnam
• Journal: Genomics
• Published: 2009;94(2):101-9
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 approximately 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.

In plain English

This was an animal experiment in mice. The authors compared normal (wild-type) mice with SPARC-null mice, which are bred to lack SPARC, a protein found in tissues undergoing remodeling. Mice had 100 micrograms of crocidolite asbestos, or saline only as a control, put into the windpipe. They were killed one week, one month or three months later. Lung RNA from about 10 mice per group was pooled and tested on arrays covering roughly 10,000 genes. The authors counted genes that differed from saline controls both significantly (p less than 0.01) and at least two-fold. At one week, 112 genes changed in SPARC-null mice versus 62 in wild-type mice. Fewer genes changed at later times. In SPARC-null mice, more genes went down than up at every time point. Mostly different genes changed at each time point. At one month these included genes in the Wnt signaling pathway. Without asbestos, the two kinds of mice differed in 61 genes. Lung scarring (fibrosis) itself was measured in a separate companion report. The authors concluded that they had identified genes that may play a role in how SPARC affects the scarring response to asbestos. They noted that pooling hides smaller changes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: microarray gene expression study of mouse lungs. Genes were kept if they differed from saline controls at p less than 0.01 and then also passed a two-fold up or down cutoff. Some genes were re-checked by real-time PCR.
• Who was studied: Female and male mice aged 6 to 8 weeks, wild-type C57Bl/6 and SPARC-null mice on a C57BL/6 background, 8 to 10 per condition and time point, University of Montana. Lung RNA from each group was pooled.
• Exposure: A single intratracheal instillation of 100 micrograms of crocidolite asbestos in 30 microliters of sterile saline (PBS). Controls received PBS only. Lungs were examined 1 week, 1 month or 3 months later.
• Main results:
  • At one week, the largest sets of changes occurred. 112 genes were up or down in SPARC-null mice compared with 62 in wild-type mice (crocidolite vs saline, significant and at least two-fold).
  • Fewer genes changed at one month and three months. Table 1 counts: wild-type 31 up and 3 down at 1 month, 44 up and 21 down at 3 months; SPARC-null 2 up and 57 down at 1 month, 7 up and 35 down at 3 months.
  • In SPARC-null mice, more genes were down-regulated than up-regulated at every time point.
  • Each time point showed a largely distinct set of altered genes.
  • Two TGF-beta-related genes, Tgfb2 and Tbrg4, were up-regulated at one week in SPARC-null mice.
  • At one month, gene groups that changed included the Wnt receptor signaling pathway.
  • At three months, gene groups that changed included lyase activity, energy production, membrane activity and transport.
  • Without asbestos, SPARC-null and wild-type lungs differed by at least two-fold in 61 genes. These included Gdf5, Sftpc, Fgf13, Saa3, Zmat3 and Wnt3.
• The authors' conclusion: The authors concluded that they had identified transcripts that may play a role in SPARC's modulation of the fibrotic response to asbestos or other stressors in the lung.
• Limitations the authors state:
  • Pooling lung RNA from about ten mice hides subtle gene expression changes, so typically only large changes are seen.

Topics

Medical terms in this study, explained in our Lexicon: Crocidolite, Fibrosis, Fibroblast.

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