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Expression of bcl-2 gene family during resection induced liver regeneration: comparison between hepatectomized and sham groups.

ABSTRACT: AIM:During liver regeneration cellular proliferation and apoptosis result in tissue remodeling to restore normal hepatic mass and structure. Main regulators of the apoptotic machinery are the Bcl-2 family proteins but their roles are not well defined throughout the liver regeneration. We aimed to analyze the expression levels of bcl-2 gene family members during resection induced liver regeneration. METHODS:We performed semi-quantitative RT-PCR to examine the expression level of bak, bax, bcl-2 and bcl-xL in 70% hepatectomized rat livers during the whole regeneration process and compared to that of the sham and normal groups. RESULTS:The expression of bak and bax was decreased whereas that of bcl-2 and bcl-xL was increased in hepatectomized animals compared to normal liver at most time points. We also reported for the first time that sham group of animals had statistically significant higher expression of bak and bax than hepatectomized animals. In addition, the area under the curve (AUC) values of these genes was larger in sham groups than the hepatectomized groups. CONCLUSION:The expression changes of bak, bax, bcl-2 and bcl-xL genes are altered not only due to regeneration, but also due to effects of surgical operations.

SUBMITTER: Akcali KC

PROVIDER: S-EPMC4717020 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature

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Expression of bcl-2 gene family during resection induced liver regeneration: comparison between hepatectomized and sham groups.

Akcali Kamil Can KC Dalgic Aydin A Ucar Ahmet A Haj Khemaeis Ben KB Guvenc Dilek D

World journal of gastroenterology 20040101 2

<h4>Aim</h4>During liver regeneration cellular proliferation and apoptosis result in tissue remodeling to restore normal hepatic mass and structure. Main regulators of the apoptotic machinery are the Bcl-2 family proteins but their roles are not well defined throughout the liver regeneration. We aimed to analyze the expression levels of bcl-2 gene family members during resection induced liver regeneration.<h4>Methods</h4>We performed semi-quantitative RT-PCR to examine the expression level of ba ...[more]

PMID: 14716839

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Project description:Hepatic expression of A20, including in hepatocytes, increases in response to injury, inflammation and resection. This increase likely serves a hepatoprotective purpose. The characteristic unfettered liver inflammation and necrosis in A20 knockout mice established physiologic upregulation of A20 as integral to the anti-inflammatory and anti-apoptotic armamentarium of hepatocytes. However, the implication of physiologic upregulation of A20 in modulating hepatocytes' proliferative responses following liver resection remains controversial. To resolve the impact of A20 on hepatocyte proliferation and the liver's regenerative capacity, we examined whether decreased A20 expression, as in A20 heterozygous knockout mice, affects outcome following two-third partial hepatectomy. A20 heterozygous mice do not demonstrate a striking liver phenotype, indicating that their A20 expression levels are still sufficient to contain inflammation and cell death at baseline. However, usually benign partial hepatectomy provoked a staggering lethality (>40%) in these mice, uncovering an unsuspected phenotype. Heightened lethality in A20 heterozygous mice following partial hepatectomy resulted from impaired hepatocyte proliferation due to heightened levels of cyclin-dependent kinase inhibitor, p21, and deficient upregulation of cyclins D1, E and A, in the context of worsened liver steatosis. A20 heterozygous knockout minimally affected baseline liver transcriptome, mostly circadian rhythm genes. Nevertheless, this caused differential expression of >1000 genes post hepatectomy, hindering lipid metabolism, bile acid biosynthesis, insulin signaling and cell cycle, all critical cellular processes for liver regeneration. These results demonstrate that mere reduction of A20 levels causes worse outcome post hepatectomy than full knockout of bona fide liver pro-regenerative players such as IL-6, clearly ascertaining A20's primordial role in enabling liver regeneration. Clinical implications of these data are of utmost importance as they caution safety of extensive hepatectomy for donation or tumor in carriers of A20/TNFAIP3 single nucleotide polymorphisms alleles that decrease A20 expression or function, and prompt the development of A20-based liver pro-regenerative therapies.

Dataset Information

Expression of bcl-2 gene family during resection induced liver regeneration: comparison between hepatectomized and sham groups.

Publications

Expression of bcl-2 gene family during resection induced liver regeneration: comparison between hepatectomized and sham groups.

Similar Datasets

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