Pathology of Gastrointestinal Organs in a Porcine Model of Cystic Fibrosis

被引:126
作者
Meyerholz, David K. [1 ]
Stoltz, David A. [2 ]
Pezzulo, Alejandro A. [2 ]
Welsh, Michael J. [2 ,3 ,4 ]
机构
[1] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA
[2] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA
[4] Univ Iowa, Roy J & Lucille A Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA
关键词
AIRWAY SUBMUCOSAL GLANDS; SMOOTH-MUSCLE-CELLS; MECONIUM ILEUS; EXOCRINE PANCREAS; INTESTINAL-OBSTRUCTION; JEJUNOILEAL ATRESIA; MURINE MODEL; DISEASE; CFTR; GENE;
D O I
10.2353/ajpath.2010.090849
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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. (Am J Pathol 2010, 176:1377-1389; DOI: 10.2353/ajpath.2010.090849)
引用
收藏
页码:1377 / 1389
页数:13
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