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Functional Analysis of Ion Transport in Liver Cyst Epithelia Combined with Proteomic Analysis of Cyst Fluid Isolated From the BALB/c‐cpk/+ Mouse Model of Polycystic Kidney Disease.
Author(s) -
Muchatuta Monalisa,
Witzmann Frank,
Gattone Vince,
BlazerYost Bonnie L.
Publication year - 2007
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.21.5.a505-b
Subject(s) - cyst , autosomal recessive polycystic kidney disease , autosomal dominant polycystic kidney disease , biology , polycystic liver disease , polycystic kidney disease , pathology , kidney , medicine , endocrinology , transplantation , liver transplantation
Liver cysts, like renal cysts, are a common finding in Autosomal Dominant (ADPKD) and Autosomal Recessive (ARPKD) Polycystic Kidney Disease in humans. Cyst growth ultimately compromises organ function. The processes involved in renal cyst formation have been well studied; however, comparatively little is known about the development and maintenance of liver cysts. The purpose of this study was to characterize the transport properties of freshly isolated liver cyst epithelia and to identify proteins in the cyst fluid. The BALB/c‐cpk/cpk mouse is a model for ARPKD and heterozygotes over a year of age exhibit hepatic cysts. Ussing‐style electrophysiological experiments on isolated cyst walls indicate a substantial portion of the basal transport rate was due to NPPB sensitive anion secretion and this was increased in response to forskolin. There was an absence of amiloride‐sensitive transport indicating that the epithelial Na + channel was not active in these epithelia. For identification, cyst fluid proteins were separated using large format 2‐dimensional gel electrophoresis. Mass spectrometry was also used to identify 48 major proteins. By gene ontology analysis, 29% of the identified proteins were transport related, of which 45% were ion transport proteins. An understanding of the mechanisms involved during formation and maintenance of liver cysts, as well as composition of the cyst fluid is necessary for development of therapeutic agents for the liver pathology associated with polycystic kidney disease.