Journal article
Pancreatic and Islet Remodeling in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Knockout Ferrets
The American journal of pathology, Vol.188(4), pp.876-890
04/2018
DOI: 10.1016/j.ajpath.2017.12.015
PMCID: PMC5963477
PMID: 29366680
Abstract
In cystic fibrosis (CF), there is early destruction of the exocrine pancreas, and this results in a unique form of diabetes that affects approximately half of adult CF individuals. An animal model of cystic fibrosis-related diabetes has been developed in the ferret, which progresses through phases of glycemic abnormalities because of islet remodeling during and after exocrine destruction. Herein, we quantified the pancreatic histopathological changes that occur during these phases. There was an increase in percentage ductal, fat, and islet area in CF ferrets over time compared with age-matched wild-type controls. We also quantified islet size, shape, islet cell composition, cell proliferation (Ki-67), and expression of remodeling markers (matrix metalloprotease-7, desmin, and α-smooth muscle actin). Pancreatic ducts were dilated with scattered proliferating cells and were surrounded by activated stellate cells, indicative of tissue remodeling. The timing of islet and duct proliferation, stellate cell activation, and matrix remodeling coincided with the previously published stages of glycemic crisis and inflammation. This mapping of remodeling events in the CF ferret pancreas provides insights into early changes that control glycemic intolerance and subsequent recovery during the evolution of CF pancreatic disease.
Details
- Title: Subtitle
- Pancreatic and Islet Remodeling in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Knockout Ferrets
- Creators
- Pavana G Rotti - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, Iowa; Department of Biomedical Engineering, The University of Iowa, Iowa City, IowaWeiliang Xie - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IowaAnanta Poudel - Department of Medicine, University of Chicago, Chicago, IllinoisYaling Yi - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IowaXingshen Sun - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IowaScott R Tyler - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IowaAliye Uc - Stead Family Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaAndrew W Norris - Stead Family Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaManami Hara - Department of Medicine, University of Chicago, Chicago, IllinoisJohn F Engelhardt - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IowaKatherine N Gibson-Corley - Department of Pathology, The University of Iowa, Iowa City, Iowa. Electronic address: katherine-gibson-corley@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.188(4), pp.876-890
- Publisher
- United States
- DOI
- 10.1016/j.ajpath.2017.12.015
- PMID
- 29366680
- PMCID
- PMC5963477
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- P30 ES005605 / NIEHS NIH HHS R24 HL123482 / NHLBI NIH HHS R01 DK097820 / NIDDK NIH HHS R24 DK096518 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS P30 DK020595 / NIDDK NIH HHS
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Biochemistry and Molecular Biology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025296302771
Metrics
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