3 years ago

Pancreatic and Islet Remodeling in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Knockout Ferrets

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 due to islet remodeling during and after exocrine destruction. Here, we quantified the pancreatic histopathologic changes that occur during these phases. There was an increase in percent ductal, fat, and islet area in CF ferrets over time compared to age-matched WT controls. We also quantified islet size, shape, islet cell composition, cell proliferation (Ki67), and expression of remodeling markers (MMP7, desmin, and SMA). 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.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017307289

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