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Hepatopancreaticobiliary pathology in the PCK model of ARPKD
Author(s) -
Mason Stephen Bruce,
EgglestonGulyas Tracy,
Lai Xianyin,
Witzmann Frank A.,
Gattone Vincent H.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.446.13
Subject(s) - pathology , bile duct , pancreatitis , medicine , choledochal cysts , biology , gastroenterology , cyst
Autosomal Recessive Polycystic Kidney Disease (ARPKD) results in renal and hepatic fibrocystic pathology. This study evaluated hepatobiliary pathology in PCK rats, an orthologous model of slowly progressive ARPKD. Male and female rats were evaluated from 4–35 weeks, quantifying organ growth, serology, bile flow rates, histology, Microfil organ casts and bile proteomics. PCK hepatofibrocystic disease is progressive (liver weight as % of body weight and hepatic fibrocystic volume), which after 18 weeks was more severe in females vs. males. A retrograde Microfil cast of hepatopancreaticobiliary ducts demonstrated widespread fusiform bile duct cysts. Pancreatic ducts open into the grossly dilated common hepatic duct. Bile flow rate for 12–15 week and 25 week PCK rats was greater than that seen in normal 15 week rats. The bile proteome from females using 2D gels identified significant differences. MS/MS protein identification of 32 spots found overexpressed proteins (triacylglycerol lipase, pancreatic amylase, chymotrypsinogen B and apolipoprotein A‐1) and numerous albumin fragments, i.e., pancreatic enzymes and fragmented proteins. Biliary pathology and proteomic findings suggest that the grossly dilated hepatic duct cause choledochal sphincter incompetence. The reflux of pancreatic enzymes into the biliary tree might exacerbate the hepatobiliary fibrosis and could also occur in human ARPKD. Grant Funding Source : NIH