Journal article
Pathology of gastrointestinal organs in a porcine model of cystic fibrosis
The American journal of pathology, Vol.176(3), pp.1377-1389
03/2010
DOI: 10.2353/ajpath.2010.090849
PMCID: PMC2832157
PMID: 20110417
Abstract
Cystic fibrosis (CF), which is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), is characterized by multiorgan pathology that begins early in life. To better understand the initial stages of disease, we studied the gastrointestinal pathology of CFTR-/- pigs. By studying newborns, we avoided secondary changes attributable to environmental interactions, infection, or disease progression. Lesions resembling those in humans with CF were detected in intestine, pancreas, liver, gallbladder, and cystic duct. These organs had four common features. First, disease was accelerated compared with that in humans, which could provide a strategy to discover modifying factors. Second, affected organs showed variable hyperplastic, metaplastic, and connective tissue changes, indicating that remodeling was a dynamic component of fetal life. Third, cellular inflammation was often mild to moderate and not always present, which raises new questions as to the role of cellular inflammation in early disease pathogenesis. Fourth, epithelial mucus-producing cells were often increased, producing a striking accumulation of mucus with a layered appearance and resilient structure. Thus, mucus cell hyperplasia and mucus accumulation play prominent roles in early disease. Our findings also have implications for CF lung disease, and they lay the foundation for a better understanding of CF pathogenesis.
Details
- Title: Subtitle
- Pathology of gastrointestinal organs in a porcine model of cystic fibrosis
- Creators
- David K Meyerholz - Department of Pathology, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. david-meyerholz@uiowa.eduDavid A StoltzAlejandro A PezzuloMichael J Welsh
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.176(3), pp.1377-1389
- DOI
- 10.2353/ajpath.2010.090849
- PMID
- 20110417
- PMCID
- PMC2832157
- NLM abbreviation
- Am J Pathol
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Publisher
- United States
- Grant note
- P01 HL091842 / NHLBI NIH HHS Howard Hughes Medical Institute HL091842 / NHLBI NIH HHS K08 AI076671 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS HL51670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS AI076671 / NIAID NIH HHS DK54759 / NIDDK NIH HHS
- Language
- English
- Date published
- 03/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020603802771
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