TLR4 knockout upregulates the expression of Mfn2 and PGC-1α in a high-fat diet and ischemia-reperfusion mice model of liver injury

Zhang, Chaoyang; Jia, Yinzhao; Liu, Bo; Wang, Guoliang

doi:10.1016/j.lfs.2020.117762

Cited by 7 publications

(7 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In NAFLD patients, soluble IL1R1 was higher (Ajmera et al, 2017). Regarding TNF signaling via NF-B in endothelial cells, in animal studies, Pecam1 KO mouse developed NASH [30], whereas Tlr4 KO mouse [31] and Il15 KO mouse [32] were protected from NAFLD. Ccr5 antagonist eased NAFLD in mice [33].…”

Section: Discussionmentioning

confidence: 96%

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Takeuchi

Liang

Shimizu-Furusawa

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Non-alcoholic fatty liver disease (NAFLD) develops from fatty liver to steatohepatitis during which multiple cell types may play different roles. Aiming to understand tissue composition of cell types, their gene expression and global gene regulation in the development of NAFLD, we performed single-nucleus and bulk ATAC-seq on the liver of rats fed with a high-fat diet (HFD). Methods Male Spontaneously Hypertensive Rats were fed a normal diet or a HFD. Rats fed HFD for 4 weeks developed fatty liver, and those fed HFD for 8 weeks further developed steatohepatitis. Under the washout condition, where 4 weeks of HFD is followed by 4 weeks of a normal diet, fatty liver was partially ameliorated. For each dietary condition, we performed single-nucleus ATAC-seq on one animal and bulk ATAC-seq on four animals. Results In accordance with the pathological progression from fatty liver to steatohepatitis, the proportion of inflammatory macrophages dramatically increased. By machine learning, we divided global gene expression into modules, such that transcription factors in a module regulate a set of genes in the same module. Consequently, many of the modules rediscovered known regulatory relationship between the transcription factors and biological processes. For the discovered biological processes, we searched core genes, which were defined as genes central regarding co-expression and protein-protein interaction. A large part of the core genes overlapped with previously implicated NAFLD genes. Conclusions Single-nucleus ATAC-seq combined with data-driven statistical analysis help elucidate the global gene regulation in vivo as a combination of modules and discover core genes of the relevant biological processes.

show abstract

Section: Discussionmentioning

confidence: 96%

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Takeuchi

Liang

Shimizu-Furusawa

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In NAFLD patients, soluble IL1R1 was higher (Ajmera et al, 2017). Regarding TNFa signaling via NF-kB in endothelial cells, in animal studies, Pecam1 KO mouse developed NASH (Goel et al, 2007), whereas Tlr4 KO mouse (Zhang et al, 2020a) (Patouraux et al, 2017). Regarding steroid metabolism in hepatocytes, Scd1 KO mouse exacerbated NAFLD (Li et al, 2009), and Acox2…”

Section: Discussionmentioning

confidence: 99%

“…In NAFLD patients, soluble IL1R1 was higher (Ajmera et al, 2017). Regarding TNFα signaling via NF-κB in endothelial cells, in animal studies, Pecam1 KO mouse developed NASH (Goel et al, 2007), whereas Tlr4 KO mouse (Zhang et al, 2020a) and Il15 KO mouse (Cepero-Donates et al, 2016) were protected from NAFLD. Ccr5 antagonist eased NAFLD in mice (Pérez-Martínez et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Takeuchi

Liang

Shimizu-Furusawa

et al. 2022

Preprint

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) develops from fatty liver to steatohepatitis during which multiple cell types may play different roles. Aiming to understand tissue composition of cell types, their gene expression and global gene regulation in the development of NAFLD, we performed single-nucleus and bulk ATAC-seq on the liver of rats fed with a high-fat diet. By machine learning, we divided global gene expression into modules, such that transcription factors in a module regulate a set of genes in the same module. Consequently, many of the modules rediscovered known regulatory relationship between the transcription factors and biological processes. For the discovered biological processes, we searched core genes, which were defined as genes central regarding co-expression and protein-protein interaction. A large part of the core genes overlapped with previously implicated NAFLD genes. Our statistical methods help elucidate the global gene regulation in vivo as a combination of modules and discover core genes of the relevant biological processes.

show abstract

“…Further evidence suggests that regulation of mitochondrial fusion may also have beneficial effects after I/R. Knocking-out toll-like receptor 4 (TLR4), a protein involved in inflammation, resulted in the upregulation of MFN2 and PGC-1α, and thus improving mitochondrial function and reducing LIRI [ 65 ]. However, amelioration of LIRI was also verified by treating mice with silibinin which decreased the levels of mitochondrial fusion-related proteins MFN1 and OPA1 [ 66 ].…”

Section: Mitochondrial Function and Dynamics During Liver I/rmentioning

confidence: 99%

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

2023

View full text Add to dashboard Cite

Liver ischemia-reperfusion injury (LIRI) is a major cause of the development of complications in different clinical settings such as liver resection and liver transplantation. Damage arising from LIRI is a major risk factor for early graft rejection and is associated with higher morbidity and mortality after surgery. Although the mechanisms leading to the injury of parenchymal and non-parenchymal liver cells are not yet fully understood, mitochondrial dysfunction is recognized as a hallmark of LIRI that exacerbates cellular injury. Mitochondria play a major role in glucose metabolism, energy production, reactive oxygen species (ROS) signaling, calcium homeostasis and cell death. The diverse roles of mitochondria make it essential to preserve mitochondrial health in order to maintain cellular activity and liver integrity during liver ischemia/reperfusion (I/R). A growing body of studies suggest that protecting mitochondria by regulating mitochondrial biogenesis, fission/fusion and mitophagy during liver I/R ameliorates LIRI. Targeting mitochondria in conditions that exacerbate mitochondrial dysfunction, such as steatosis and aging, has been successful in decreasing their susceptibility to LIRI. Studying mitochondrial dysfunction will help understand the underlying mechanisms of cellular damage during LIRI which is important for the development of new therapeutic strategies aimed at improving patient outcomes. In this review, we highlight the progress made in recent years regarding the role of mitochondria in liver I/R and discuss the impact of liver conditions on LIRI.

show abstract

TLR4 knockout upregulates the expression of Mfn2 and PGC-1α in a high-fat diet and ischemia-reperfusion mice model of liver injury

Cited by 7 publications

References 52 publications

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

Contact Info

Product

Resources

About