Journal article
Pancreatic Damage in Fetal and Newborn Cystic Fibrosis Pigs Involves the Activation of Inflammatory and Remodeling Pathways
The American journal of pathology, Vol.181(2), pp.499-507
08/2012
DOI: 10.1016/j.ajpath.2012.04.024
PMCID: PMC3409440
PMID: 22683312
Abstract
Pancreatic disease has onset
in utero
in humans with cystic fibrosis (CF), and progresses over time to complete destruction of the organ. The exact mechanisms leading to pancreatic damage in CF are incompletely understood. Inflammatory cells are present in the pancreas of newborn pigs with CF (CF pigs) and humans, which suggests that inflammation may have a role in the destructive process. We wondered whether tissue inflammation and genes associated with inflammatory pathways were increased in the pancreas of fetal CF pigs [83 to 90 days gestation (normal pig gestation is ∼114 days)] and newborn pigs. Compared with fetal pigs without CF (non-CF pigs), in fetal CF pigs, the pancreas exhibited patchy inflammation and acinar atrophy, with progression in distribution and severity in neonatal CF pigs. Large-scale transcript profiling revealed that the pancreas in fetal and newborn CF pigs exhibited significantly increased expression of proinflammatory, complement cascade, and profibrotic genes when compared with fetal and newborn non-CF pigs. Acinar cells exhibited increased apoptosis in the pancreas of fetal and newborn CF pigs. α-Smooth muscle actin and transforming growth factor β1 were increased in both fetal and newborn CF pig pancreas, suggesting activation of profibrotic pathways. Cell proliferation and mucous cell metaplasia were detected in newborn, but not fetal, CF pigs, indicating that they were not an initiator of pathogenesis but a response. Proinflammatory, complement cascade, proapoptotic, and profibrotic pathways are activated in CF pig pancreas, and likely contribute to the destructive process.
Details
- Title: Subtitle
- Pancreatic Damage in Fetal and Newborn Cystic Fibrosis Pigs Involves the Activation of Inflammatory and Remodeling Pathways
- Creators
- Maisam Abu-El-Haija - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaShyam Ramachandran - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaDavid K Meyerholz - Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IowaMarwa Abu-El-Haija - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaMichelle Griffin - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaRadhamma L Giriyappa - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaDavid A Stoltz - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IowaMichael J Welsh - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IowaPaul B McCray - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaAliye Uc - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.181(2), pp.499-507
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.1016/j.ajpath.2012.04.024
- PMID
- 22683312
- PMCID
- PMC3409440
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Language
- English
- Date published
- 08/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020762702771
Metrics
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