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The rat lncRNA and mRNA microarray analysis of the 6 samples from2-AAF/PH group and Diwu Yanggan capsule treatment group

ABSTRACT: In some previous studies, DWYG played key roles in improving immune-modulatory responses, ameliorating liver lesions, enhancing liver regeneration, virus-killing activities and HCC inhibition. It has been shown that liver injury caused by an array of factors, can significantly hinder the regenerative effects of mature hepatocytes on liver parenchyma. However, factors such as 2-acetylaminofluorene (2-AAF) induce hepatocyte injury to limit the regenerative ability of liver. In addition, 2-AAF exposure results in cell lysis and disrupts other liver functions. These have made the 2-AAF/PH animal model the most commonly used in assessing the mechanisms by which medicines exert therapeutic effects. In our previous study, it has been demonstrated that DWYG could control HCC in 2-AAF/PH rats, potentially through the modulation and restoration of the liver regeneration microenvironment.However, the comprehensive mechanisms of 2-AAF/PH-induced rat pathogenesis and the pharmacological mechanisms of DWYG is still poorly understood. The present study there aims to explore the mechanisms by which DWYG regulates hepatic transcriptome in a 2-AAF/PH-induced rat model in view of enhancing its applications in liver treatment.

ORGANISM(S): Mus musculus Rattus norvegicus

PROVIDER: GSE151614 | GEO | 2020/06/03

REPOSITORIES: GEO

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Project description:Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency (i.e., the ability to recover from injury) and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical mitogenic and morphogenic functions during development. Recent studies indicate that Hedgehog regulates metabolic homeostasis in adult liver. The present study evaluates the hypothesis that Hedgehog signaling becomes dysregulated in hepatocytes during aging, resulting in decreased resiliency and therefore, impaired regeneration and enhanced vulnerability to damage. Methods: Partial hepatectomy (PH) was performed on young and old wild type mice and Smoothened (Smo)-floxed mice treated with AAV8-TBG luciferase (control) or AAV8-TBG-Cre vectors to conditionally delete Smo and disrupt Hedgehog signaling specifically in hepatocytes. Changes in signaling were correlated with changes in regenerative responses and compared among groups. Results: Old livers had fewer hepatocytes proliferating after PH. RNA sequencing identified Hedgehog as a top down-regulated pathway in old hepatocytes before and after the regenerative challenge. Deleting Smo in healthy young hepatocytes before PH prevented Hedgehog pathway activation after PH and inhibited regeneration. GO analysis demonstrated that both old and Smo-deleted young hepatocytes had activation of pathways involved in innate immune responses and suppression of several signaling pathways that control liver growth and metabolism including insulin-like growth factor, Wnt and NOTCH. Hedgehog inhibition promoted telomere shortening and mitochondrial dysfunction in hepatocytes, consequences of aging that promote inflammation and impair tissue growth and metabolic homeostasis. Conclusion: Hedgehog signaling is dysregulated in old hepatocytes. This accelerates aging, resulting in decreased resiliency and therefore, impaired liver regeneration and enhanced vulnerability to damage.

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The rat lncRNA and mRNA microarray analysis of the 6 samples from2-AAF/PH group and Diwu Yanggan capsule treatment group

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