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81 Publications visible to you, out of a total of 81
Capsaicin receptor TRPV1 maintains quiescence of hepatic stellate cells in the liver via recruitment of SARM1

Abstract

Not specified

Authors: Le Tao, Guangyue Yang, Tiantian Sun, Jie Tao, Chan Zhu, Huimin Yu, Yalan Cheng, Zongguo Yang, Mingyi Xu, Yuefeng Jiang, Wei Zhang, Zhiyi Wang, Wenting Ma, Liu Wu, Dongying Xue, Dongxue Wang, Wentao Yang, Yongjuan Zhao, Shane Horsefield, Bostjan Kobe, Zhe Zhang, Zongxiang Tang, Qigen Li, Qiwei Zhai, Steven Dooley, Ekihiro Seki, Ping Liu, Jianrong Xu, Hongzhuan Chen, Cheng Liu

Date Published: 2023

Publication Type: Journal

Caveolin-1 Impacts on TGF-beta Regulation of Metabolic Gene Signatures in Hepatocytes.

Abstract (Expand)

Caveolin-1 (CAV1) is a membrane protein associated with metabolism in various cell types. The transforming growth factor beta (TGF-beta) is a pro-fibrogenic cytokine in the liver, but its metabolic … gene signatures remain unclear to date. We have previously shown that CAV1 alters TGF-beta signaling and blocks its pro-apoptotic function. Here, we defined TGF-beta-induced metabolic gene signatures in hepatocytes and assessed whether CAV1 abundance affects TGF-beta control of those metabolic genes. Microarray analyses of primary hepatocytes after TGF-beta stimulation (48 h) showed differential expression of 4224 genes, of which 721 are metabolic genes (adjusted p < 0.001). Functional annotation analysis revealed that TGF-beta mainly suppresses metabolic gene network, including genes involved in glutathione, cholesterol, fatty acid, and amino acid metabolism. TGF-beta also upregulated several genes related to glycan metabolism and ion transport. In contrast to TGF-beta effects, CAV1 knockdown triggered the upregulation of metabolic genes. Immortalized mouse hepatocytes (AML12 cells) were used to validate the gene changes induced by TGF-beta stimulation and CAV1 knockdown. Noteworthy, of the TGF-beta metabolic target genes, CAV1 modulated the expression of 228 (27%). In conclusion, we present several novel metabolic gene signatures of TGF-beta in hepatocytes and show that CAV1 abundance alters almost a third of these genes. These findings could enable a better understanding of TGF-beta function in normal and diseased liver especially where differential CAV1 level is implicated.

Authors: M. Han, Z. C. Nwosu, W. Pioronska, M. P. Ebert, S. Dooley, C. Meyer

Date Published: 22nd Feb 2020

Publication Type: Journal

Caveolin-1 in the regulation of cell metabolism: a cancer perspective.

Abstract (Expand)

Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and signaling. Recent studies reveal that … CAV1 is involved in metabolic alterations - a critical strategy adopted by cancer cells to their survival advantage. Consequently, research findings suggest that CAV1, which is altered in several cancer types, influences tumour development or progression by controlling metabolism. Understanding the molecular interplay between CAV1 and metabolism could help uncover druggable metabolic targets or pathways of clinical relevance in cancer therapy. Here we review from a cancer perspective, the findings that CAV1 modulates cell metabolism with a focus on glycolysis, mitochondrial bioenergetics, glutaminolysis, fatty acid metabolism, and autophagy.

Authors: Z. C. Nwosu, M. P. Ebert, S. Dooley, C. Meyer

Date Published: 18th Nov 2016

Publication Type: Not specified

Cellular and nuclear hepatocyte ploidy represent a repository in regenerating livers

Abstract

Not specified

Authors: S Hammad, U Dahmen, A Othman, I Recklinghausen, JG Hengstler, U Klingmüller, S Dooley

Date Published: 2019

Publication Type: Not specified

Cold shock protein YB-1 upregulates MDR1 transcription and thus contributes to cholangiocarcinoma chemoresistance to cisplatin

Abstract

Not specified

Authors: Tao Lin, Heng Liu, Jon Lindquist, Peter Mertens, Matthias Ebert, Steven Dooley, Jun Li, Stefan Munker, Honglei Weng

Date Published: 2022

Publication Type: Journal

Computational Modeling in Liver Surgery

Abstract (Expand)

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection … strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

Authors: Bruno Christ, Uta Dahmen, Karl-Heinz Herrmann, Matthias König, Jürgen R. Reichenbach, Tim Ricken, Jana Schleicher, Lars Ole Schwen, Sebastian Vlaic, Navina Waschinsky

Date Published: 14th Nov 2017

Publication Type: Not specified

Cooperative and distinct functions of MK2 and MK3 in the regulation of the macrophage transcriptional response to lipopolysaccharide.

Abstract (Expand)

The p38(MAPK) downstream targets MAPKAP kinases (MK) 2 and 3 are critical for the regulation of the macrophage response to LPS. The extents to which these two kinases act cooperatively and distinctly … in regulating LPS-induced inflammatory cytokine expression are still unclear. To address this uncertainty, whole transcriptome analyses were performed using bone marrow-derived macrophages (BMDM) generated from MK2(-/-) or MK2/3(-/-) animals and their wild-type littermates. The results suggest that in BMDM, MK2 and MK3 not only cooperatively regulate the transcript expression of signaling intermediates, including IL-10, IL-19, CXCL2 and the IL-4 receptor (IL-4R)alpha subunit, they also exert distinct regulatory effects on the expression of specific transcripts. Based on the differential regulation of gene expression by MK2 and MK3, at least six regulatory patterns were identified. Importantly, we confirmed our previous finding, which showed that in the absence of MK2, MK3 negatively regulates IFN-beta. Moreover, this genome-wide analysis identified the regulation of Cr1A, NOD1 and Serpina3f as similar to that of IFN-beta. In the absence of MK2, MK3 also delayed the nuclear translocation of NFkappaB by delaying the ubiquitination and subsequent degradation of IkappaBbeta, reflecting the substantial plasticity of the response of BMDM to LPS.

Authors: C. Ehlting, J. Rex, U. Albrecht, R. Deenen, C. Tiedje, K. Kohrer, O. Sawodny, M. Gaestel, D. Haussinger, J. G. Bode

Date Published: 30th Jul 2019

Publication Type: Not specified

Creation of Three-Dimensional Liver Tissue Models from Experimental Images for Systems Medicine.

Abstract (Expand)

In this chapter, we illustrate how three-dimensional liver tissue models can be created from experimental image modalities by utilizing a well-established processing chain of experiments, microscopic … imaging, image processing, image analysis and model construction. We describe how key features of liver tissue architecture are quantified and translated into model parameterizations, and show how a systematic iteration of experiments and model simulations often leads to a better understanding of biological phenomena in systems biology and systems medicine.

Authors: S. Hoehme, A. Friebel, S. Hammad, D. Drasdo, J. G. Hengstler

Date Published: 11th Nov 2016

Publication Type: Not specified

CYP2E1 recovery is associated with a pericentral fibrosis pattern after repeated CCl4 insults

Abstract

Not specified

Authors: S Hammad, J Zhao, Y Yin, A Zaza, D Drasdo, JG Hengstler, S Dooley

Date Published: 2019

Publication Type: Not specified

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