Lack of Guanylate Cyclase C results in increased mortality in mice following liver injuryReport as inadecuate

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BMC Gastroenterology

, 10:86

First Online: 02 August 2010Received: 15 January 2010Accepted: 02 August 2010


BackgroundGuanylate Cyclase C GC-C expression in the intestine plays a role in the regulation of fluid and ion transport, as well as epithelial cell apoptosis and proliferation. In the adult rat liver, GC-C expression is increased in response to injury. We hypothesized that GC-C is required for repair-recovery from liver injury.

MethodsWe subjected wild type WT and GC-C deficient mice to acute liver injury with a single injection of the hepatotoxin carbon tetrachloride. Changes in the level of expression of GC-C and its ligands uroguanylin and guanylin were quantified by real-time PCR. Liver morphology, and hepatocyte necrosis, apoptosis and proliferation, were examined at 1-3 days post-injury in mice on a mixed genetic background. Survival was followed for 14 days after carbon tetrachloride injection in wild type and GC-C deficient mice on both a mixed genetic background and on an inbred C57BL6-J background.

ResultsGC-C deficient mice on the mixed genetic background nearly all died median survival of 5 days following carbon tetrachloride injection while WT littermates experienced only 35% mortality. Elevated levels of TUNEL-positive hepatocyte death on post-injury day 1, increased apoptosis on day 2, and increased areas of centrilobular necrosis on days 2 and 3, were evident in livers from GC-C null mice compared to WT. Collectively these data suggest increased hepatocyte death in the GC-C null mice in the early time period after injury. This corresponds temporally with increased expression of GC-C and its ligands guanylin and uroguanylin in post-injury WT mouse liver. The hepatocyte proliferative response to injury was the same in both genotypes. In contrast, there was no difference in survival between GC-C null and WT mice on the inbred C57BL-6 J background in response to acute liver injury.

ConclusionsSignalling via GC-C promotes hepatocyte survival in vivo and is required for effective recovery from acute toxic injury to the liver in a strain-specific manner.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-230X-10-86 contains supplementary material, which is available to authorized users.

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Author: Elizabeth A Mann - Kumar Shanmukhappa - Mitchell B Cohen


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