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Differential Aquaporin Expression in Hepatic Stellate Cells During Transdifferentiation
Author(s) -
Lakner Ashley,
Gulledge Alyssa,
McKillop Iain,
Schrum Laura
Publication year - 2009
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.23.1_supplement.981.6
Subject(s) - hepatic stellate cell , apoptosis , aquaporin , transdifferentiation , western blot , microbiology and biotechnology , cell culture , cell growth , chemistry , biology , endocrinology , stem cell , biochemistry , gene , genetics
Persistent activation and increased cell survival of the hepatic stellate cell (HSC) leads to the development and progression of liver fibrosis. Induction of HSC apoptosis and decreased proliferation can attenuate fibrosis. Aquaporins (AQP) play a critical role in both the initiation of apoptosis and proliferation. The expression profile and function of AQPs have not been determined in the daily progression of HSC activation. AQP 0, 1, 5, 8, 9, 11 and 12 mRNAs were detected in freshly isolated (dQ) cells, while activated (d14) cells exhibited a marked decrease in expression as demonstrated by semiquantitative and RealTime PCR. However, AQP mRNA expression profiles showed transient increases during culture activation (d1‐d10). Western blot analyses showed decreased AQP 8 and 9 protein expression in d14 versus dQ cells. Osmotic challenge significantly increased cell swelling in dQ cells which was abolished by pre‐treatment with HgCl 2 , an AQP channel blocker, while d14 cells did not swell. D1 and d14 HSCs exhibited decreased cellular viability after one hour exposure to the apoptotic agent gliotoxin, whereas dQ cells responded within 20 minutes. HgCl 2 pretreatment abrogated these effects. These data suggest that HSC survival may be modulated by AQP expression which could be a potential therapeutic target. Supported by NIH AA14891.