Inhibition of autophagy and Hsp90 activity alleviate metabolic and infectious diseases by regulating hepatic lipid deposition and ROS accumulation in zebrafish larvae with hepatobiliary syndrome and/or GCRV-II infection
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ABSTRACT:
PROVIDER: PRJNA1152566 | ENA |
REPOSITORIES: ENA
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Project description:Hepatobiliary syndrome is caused by the impairment of liver fat metabolism in fish, which leads to the weakening or loss of hepatobiliary function. Also, metabolic hepatobiliary syndrome leads to low immune resistance of diseased fish, which is easily induce fish to be infected with other bacterial or viral diseases. By treating wild-type zebrafish larvae with different concentrations of dexamethasone, we found that dexamethasone induced hepatomegaly, hepatic lipid deposition and reduced survival in zebrafish. In addition, dexamethasone treatment combined with GCRV-II infection aggravated lipid deposition in the liver and impaired the survival of zebrafish larvae. Transcriptome data showed that autophagy signaling pathways and blood pressure regulation pathways are significantly enriched. Furthermore, we treated zebrafish larvae with autophagy inhibitor and HSP90 inhibitor, dexamethasone and GCRV-II infection, then found that the survival of zebrafish larvae was improved, liver lipid deposition was attenuated, and ROS production was greatly reduced. In conclusion, this study provides insights into the regulation of immune metabolism in zebrafish hepatobiliary syndrome and GCRV-II infection, and provides potential molecular targets for the prevention and control of metabolic disease-induced infectious diseases in other cyprinids.
2025-08-28 | GSE275683 | GEO
Project description:Hepatocyte nuclear factor 4β (Hnf4β), a nuclear receptor superfamily member, acts as a key regulator of functional gene expression and various cellular processes. The function of Hnf4β in metabolic diseases or infectious diseases had not yet defined in teleost. Here, we show that zebrafish Hnf4β plays a protective role in the host defense against dexamethasone (DEX)-induced hepatobiliary syndrome and hepatobiliary syndrome complicated with GCRV-II infection. Zebrafish Hnf4β deficiency have hepatomegaly, lipid deposition, impairs larvae survival and regulates the expression levels of many genes involved in oxidative phosphorylation and spliceosome during DEX treatment plus GCRV-II infection. In addition, Hnf4β gene disruption in zebrafish leads to induction of oxidative stress with the increased susceptibility to dexamethasone-induced hepatobiliary syndrome complicated with GCRV-II infection. Furthermore, we show that zebrafish Hsp70 promote the translocation of Hnf4β from the nucleus to the cytoplasm and interact with Hnf4β in the cytoplasm and nucleus at DEX + GCRV situation. Mechanistically, zebrafish Hnf4β mediates the beneficial effect for larvae survival and lipid metabolism in the case of DEX treatment plus GCRV-II infection is depending on the Hsp70-mediated autophagy. Collectively, our results identify that the mechanisms of zebrafish Hnf4β through targeting Hsp70 against dexamethasone-induced hepatobiliary syndrome complicated with GCRV-II infection.
2026-01-01 | GSE303991 | GEO
Project description:Hepatocyte nuclear factor 4β protect zebrafish from dexamethasone-induced hepatobiliary syndrome and hepatobiliary syndrome complicated with GCRV-II infection by targeting Hsp70 and inhibiting autophagy
| PRJNA1298598 | ENA
Project description:Few studies reported for obtaining the grass carp resistant to hemorrhagic disease via gene editing in commercial fish. Here, we demonstrate that the expression and activity of grass carp PI4KB (gcPI4KB) are vital for GCRV-I and GCRV-II replication. Due that obvious cytopathic effect (CPE) in the present available cell lines is only caused by GCRV-I, but GCRV-II is the current popular and fatal strain in grass carp, GCRV-I and GCRV-II are used in cell lines and in grass carp, respectively. The in vitro studies in CIK cells revealed that gcPI4KB interacted with NS80 and VP3 of GCRV-I, and that gcPI4KB was recruited by NS80 for promoting the generation of GCRV VIBs. Since the negative regulatory role of gcPI4KB in GCRV infection was confirmed by in vitro data,we performed gene editing of gcPI4KB in grass carp. We found that PI4KB F0 crispants juvenile grass carp have obvious advantages in promoting growth and in resisting GCRV-II infection. Compared with uninfected WT grass carp, the uninfected PI4KB F0 crispants juvenile grass carp exhibit a higher expression level of many genes involved in growth- and development-related metabolic pathways such as the FoxO signaling pathway and insulin signaling pathway. Compared with WT grass carp without infection, PI4KB F0 crispants juvenile grass carp without infection or WT grass carp infected with GCRV-II, higher expression levels for many genes involved in metabolic diseases and viral infection were observed in the liver from PI4KB F0 crispants juvenile grass carp infected with GCRV-II. Altogether, the present study suggests the mechanism of gcPI4KB in facilitating GCRV replication, the signaling pathways regulated by gcPI4KB, and the possibility to obtain the grass carp resistant to hemorrhagic disease via gene editing of PI4KB.
2025-09-30 | GSE273923 | GEO
Project description:HSP70 of grass carp and outer capsid protein VP7 of GCRV determines the early stage of viral entry. Multi-transcriptomic analysis identified HSP70 as a key player in the pathogenesis of GCRV infection. Temperature-dependent, and primarily plasma membrane anchored HSP70 interacts with VP7 to facilitate viral entry during the early phase of GCRV infection. We indentified the interaction of vp7 and hsp70 by MS.
2023-05-09 | PXD036008 | Pride
Project description:This project is to identify plasma glycoprotein markers for hepatobiliary cancers
2019-11-12 | PXD013629 | Pride
Project description:Hsp90 is a molecular chaperone involved in the regulation and maturation of kinases and transcription factors. In Caenorhabditis elegans, it contributes to the development of fertility, maintenance of muscle structure, the regulation of heat-shock response and dauer state. To understand the consequences of Hsp90-depletion, we studied Hsp90 RNAi-treated nematodes by DNA microarrays and mass spectrometry. We find that upon development of phenotypes the levels of chaperones and Hsp90 cofactors are increased, while specific proteins related to the innate immune response are depleted. In microarrays, we further find many differentially expressed genes related to gonad and larval development. These genes form an expression cluster that is regulated independently from the immune response implying separate pathways of Hsp90-involvement. Using fluorescent reporter strains for the differentially expressed immune response genes skr-5, dod-24 and clec-60 we observe that their activity in intestinal tissues is influenced by Hsp90-depletion. Instead, effects on the development are evident in both gonad arms. After Hsp90-depletion, changes can be observed in early embryos and adults containing fluorescence-tagged versions of SEPA-1, CAV-1 or PUD-1, all of which are downregulated after Hsp90-depletion. Our observations identify molecular events for Hsp90-RNAi induced phenotypes during development and immune responses, which may help to separately investigate independent Hsp90-influenced processes that are relevant during the nematode’s life and development. We used microarrays to detail the global programme of gene expression after RNAi-mediated Hsp90 knock-down.
2017-10-17 | GSE105030 | GEO
Project description:This project is to identify plasma glycoprotein markers for hepatobiliary cancers
2020-08-31 | MSV000086047 | MassIVE
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
2023-03-11 | PXD028822 | Pride
Project description:The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a unique role promoting the evolution of new heritable traits. To better understand how Hsp90 can affect mRNA translation we screened more than 1600 factors involved in mRNA regulation for physical interactions with Hsp90 in human cells. The mRNA binding protein CPEB2 strongly binds Hsp90 via its prion domain. In a yeast model, transient inhibition of Hsp90 resulted in persistent activation of a CPEB translation reporter even in the absence of exogenous CPEB that persisted for 30 generations after the inhibitor was removed. Ribosomal profiling revealed that some endogenous yeast mRNAs, including HAC1, show a persistent change in translation efficiency following transient Hsp90 inhibition. Thus, transient loss of Hsp90 function can promote a non-genetic inheritance of a translational state affecting specific mRNAs, introducing a new mechanism by which Hsp90 can promote phenotypic variation.
2020-08-11 | GSE153945 | GEO