scholarly journals c-Met Signaling Protects from Nonalcoholic Steatohepatitis- (NASH-) Induced Fibrosis in Different Liver Cell Types

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Hannah K. Drescher ◽  
Fabienne Schumacher ◽  
Teresa Schenker ◽  
Maike Baues ◽  
Twan Lammers ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stress Response ◽  
Kupffer Cells ◽  
Liver Cell ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Types ◽  
Oxidative Stress Response ◽  
Cell Type

Nonalcoholic steatohepatitis (NASH) is the most common chronic, progressive liver disease in Western countries. The significance of cellular interactions of the HGF/c-Met axis in different liver cell subtypes and its relation to the oxidative stress response remains unclear so far. Hence, the present study is aimed at investigating the role of c-Met and the interaction with the oxidative stress response during NASH development in mice and humans. Conditional c-Met knockout (KO) lines (LysCre for Kupffer cells/macrophages, GFAPCre for α-SMA+ and CK19+ cells and MxCre for bone marrow-derived immune cells) were fed chow and either methionine-choline-deficient diet (MCD) for 4 weeks or high-fat diet (HFD) for 24 weeks. Mice lacking c-Met either in Kupffer cells, α-SMA+ and CK19+ cells, or bone marrow-derived immune cells displayed earlier and faster progressing steatohepatitis during dietary treatments. Severe fatty liver degeneration and histomorphological changes were accompanied by an increased infiltration of immune cells and a significant upregulation of inflammatory cytokine expression reflecting an earlier initiation of steatohepatitis development. In addition, animals with a cell-type-specific deletion of c-Met exhibited a strong generation of reactive oxygen species (ROS) by dihydroethidium (hydroethidine) (DHE) staining showing a significant increase in the oxidative stress response especially in LysCre/c-Metmut and MxCre/c-Metmut animals. All these changes finally lead to earlier and stronger fibrosis progression with strong accumulation of collagen within liver tissue of mice deficient for c-Met in different liver cell types. The HGF/c-Met signaling pathway prevents from steatosis development and has a protective function in the progression to steatohepatitis and fibrosis. It conveys an antifibrotic role independent on which cell type c-Met is missing (Kupffer cells/macrophages, α-SMA+ and CK19+ cells, or bone marrow-derived immune cells). These results highlight a global protective capacity of c-Met in NASH development and progression.

scholarly journals Chronic stress induces co-ordinated cortical microcircuit cell type transcriptomic changes consistent with altered information processing

2020 ◽  
Author(s):  
Dwight F. Newton ◽  
Hyunjung Oh ◽  
Rammohan Shukla ◽  
Keith Misquitta ◽  
Corey Fee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Information Processing ◽  
Stress Response ◽  
Cell Function ◽  
Cell Types ◽  
Brain Regions ◽  
Oxidative Stress Response ◽  
Dendritic Morphology ◽  
Mild Stress ◽  
Cell Type

ABSTRACTMajor depressive disorder (MDD) is associated with altered GABAergic and glutamatergic signalling, suggesting altered excitation-inhibition balance (EIB) in cortical mood- and cognition-regulating brain regions. Information processing in cortical microcircuits involves regulation of pyramidal (PYR) cells by Somatostatin-(SST), Parvalbumin-(PV), and Vasoactive intestinal peptide-(VIP) expressing interneurons. Human and rodent studies suggest that impaired PYR-cell dendritic morphology and decreased SST-cell function may mediate altered EIB in MDD. However, knowledge of co-ordinated changes across microcircuit cell types is virtually absent. We thus investigated the co-ordinated transcriptomic effects of UCMS on microcircuit cell types in the medial prefrontal cortex. C57Bl/6 mice, exposed to unpredictable chronic mild stress (UCMS) or control housing for five weeks were assessed for anxiety- and depressive-like behaviours. Microcircuit cell types were laser-microdissected and processed for RNA-sequencing. UCMS-exposed mice displayed predicted elevated behavioural emotionality. Each microcircuit cell type showed a unique transcriptional signature after UCMS. Pre-synaptic functions, oxidative stress response, metabolism, and translational regulation were differentially dysregulated across cell types, whereas nearly all cell types showed down-regulated post-synaptic gene signatures. At the microcircuit level, we observed a shift from distributed transcriptomic co-ordination across cell types in controls towards UCMS-induced increased co-ordination between PYR-, SST- and PV-cells, and a hub-like role for PYR-cells. Lastly, we identified a microcircuit-wide co-expression network enriched in synaptic, bioenergetic, and oxidative stress response genes that correlated with UCMS-induced behaviours. Together, these findings suggest cell-specific deficits, microcircuit-wide synaptic reorganization, and a shift in cortical EIB mediated by increased co-ordinated regulation of PYR-cells by SST- and PV-cells.

scholarly journals PCB congener specific oxidative stress response by microarray analysis using human liver cell line

2010 ◽  
Vol 36 (8) ◽  
pp. 907-917 ◽  
Author(s):  
Supriyo De ◽  
Somiranjan Ghosh ◽  
Raghunath Chatterjee ◽  
Y-Q Chen ◽  
Linda Moses ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Cell Line ◽  
Microarray Analysis ◽  
Liver Cell ◽  
Human Liver ◽  
Oxidative Stress Response ◽  
Liver Cell Line ◽  
Human Liver Cell

scholarly journals Yersiniabactin Reduces the Respiratory Oxidative Stress Response of Innate Immune Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8240 ◽  
Author(s):  
Armand Paauw ◽  
Maurine A. Leverstein-van Hall ◽  
Kok P. M. van Kessel ◽  
Jan Verhoef ◽  
Ad C. Fluit
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Immune Cells ◽  
Oxidative Stress Response ◽  
Innate Immune ◽  
Innate Immune Cells

scholarly journals Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress

2021 ◽  
Vol 9 (6) ◽  
pp. 1116
Author(s):  
Laurens Maertens ◽  
Pauline Cherry ◽  
Françoise Tilquin ◽  
Rob Van Houdt ◽  
Jean-Yves Matroule
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Stress Responses ◽  
Caulobacter Crescentus ◽  
Oxidative Stress Response ◽  
Transport Systems ◽  
Transcriptomic Response ◽  
Swarmer Cell ◽  
Cu Stress ◽  
Cellular Environment

Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation.

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