Role of fibroblast growth factor signalling in hepatic fibrosis

Seitz, Tatjana; Hellerbrand, Claus

doi:10.1111/liv.14863

Cited by 47 publications

(40 citation statements)

References 142 publications

(335 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A possible reason could be the counteracting effects of BMP2 (present in healthy and regenerating samples), a molecule important in resolving liver fibrosis 35 . In addition, FGF family members were higher expressed in the regenerating cells, consistent with other tissue repair processes 36 . Also, in the TGF superfamily of proteins, INHBA signaling was solely captured in the regenerating tissue.…”

Section: The Immune Compartment Has a Pivotal Role In Modulating Liver Response To Pvesupporting

confidence: 73%

Cell atlas of the regenerating human liver after portal vein embolization

Brazovskaja

Gomes

Körner

et al. 2021

Preprint

View full text Add to dashboard Cite

The liver has the remarkable capacity to regenerate. In the clinic, this capacity can be induced by portal vein embolization (PVE), which redirects portal blood flow resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the liver during regeneration. We first establish an atlas of cell subtypes from the healthy human liver using fresh and frozen tissues, and then compare post-PVE samples with their reference counterparts. We find that PVE alters portal-central zonation of hepatocytes and endothelial cells. Embolization upregulates expression programs associated with development, cellular adhesion and inflammation across cell types. Analysis of interlineage crosstalk revealed key roles for immune cells in modulating regenerating tissue responses. Altogether, our data provides a rich resource for understanding homeostatic mechanisms arising during human liver regeneration and degeneration.

show abstract

Section: The Immune Compartment Has a Pivotal Role In Modulating Liver Response To Pvesupporting

confidence: 73%

Cell atlas of the regenerating human liver after portal vein embolization

Brazovskaja

Gomes

Körner

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The most significantly enriched pathway in Reactome pathway analysis, signaling by receptor tyrosine kinases, was also recently reported to be associated with liver fibrosis. Fibroblast growth factor receptor, a major family of receptor tyrosine kinases, plays a key role in the progression and resolution of liver fibrosis by interacting with HSCs, hepatocytes and immune cells ( Seitz & Hellerbrand, 2021 ). In addition, knockdown of Gab1 , an important protein in the receptor tyrosine kinase pathway, significantly exacerbated liver fibrosis in animal models ( Mizutani et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA-target gene regulatory networks in liver fibrosis based on bioinformatics analysis

Tai

Zhao

Gao

et al. 2021

PeerJ

View full text Add to dashboard Cite

Background Liver cirrhosis is one of the leading causes of death worldwide. MicroRNAs (miRNAs) can regulate liver fibrosis, but the underlying mechanisms are not fully understood, and the interactions between miRNAs and mRNAs are not clearly elucidated. Methods miRNA and mRNA expression arrays of cirrhotic samples and control samples were acquired from the Gene Expression Omnibus database. miRNA-mRNA integrated analysis, functional enrichment analysis and protein-protein interaction (PPI) network construction were performed to identify differentially expressed miRNAs (DEMs) and mRNAs (DEGs), miRNA-mRNA interaction networks, enriched pathways and hub genes. Finally, the results were validated with in vitro cell models. Results By bioinformatics analysis, we identified 13 DEMs between cirrhotic samples and control samples. Among these DEMs, six upregulated (hsa-miR-146b-5p, hsa-miR-150-5p, hsa-miR-224-3p, hsa-miR-3135b, hsa-miR-3195, and hsa-miR-4725-3p) and seven downregulated (hsa-miR-1234-3p, hsa-miR-30b-3p, hsa-miR-3162-3p, hsa-miR-548aj-3p, hsa-miR-548x-3p, hsa-miR-548z, and hsa-miR-890) miRNAs were further validated in activated LX2 cells. miRNA-mRNA interaction networks revealed a total of 361 miRNA-mRNA pairs between 13 miRNAs and 245 corresponding target genes. Moreover, PPI network analysis revealed the top 20 hub genes, including COL1A1, FBN1 and TIMP3, which were involved in extracellular matrix (ECM) organization; CCL5, CXCL9, CXCL12, LCK and CD24, which participated in the immune response; and CDH1, PECAM1, SELL and CAV1, which regulated cell adhesion. Functional enrichment analysis of all DEGs as well as hub genes showed similar results, as ECM-associated pathways, cell surface interaction and adhesion, and immune response were significantly enriched in both analyses. Conclusions We identified 13 differentially expressed miRNAs as potential biomarkers of liver cirrhosis. Moreover, we identified 361 regulatory pairs of miRNA-mRNA and 20 hub genes in liver cirrhosis, most of which were involved in collagen and ECM components, immune response, and cell adhesion. These results would provide novel mechanistic insights into the pathogenesis of liver cirrhosis and identify candidate targets for its treatment.

show abstract

“…Fibroblast growth factor (FGF) signaling is a prerequisite for adequate would healing, repair and homeostasis in various tissues and organs (Seitz and Hellerbrand, 2021). Since liver fibrosis is a wound healing response to liver injury, FGFs play an important role in hepatic fibrosis by acting as paracrine, and endocrine mediators of hepatocyte regeneration and HSC migration, proliferation and trans-differentiation (Schumacher and Guo, 2016).…”

Section: Fibroblast Growth Factor Signalingmentioning

confidence: 99%

“…Since liver fibrosis is a wound healing response to liver injury, FGFs play an important role in hepatic fibrosis by acting as paracrine, and endocrine mediators of hepatocyte regeneration and HSC migration, proliferation and trans-differentiation (Schumacher and Guo, 2016). The paracrine FGFs (FGF1-10, FGF16-18, FGF20 and FGF22) bind strongly to heparan sulphate proteoglycans, which limits FGF diffusion through ECM and restricts their action to the site of secretion (Ornitz and Itoh, 2015;Seitz and Hellerbrand, 2021). The three endocrine FGFs, FGF19 (mouse homolog FGF15), FGF21 and FGF23 participate in phosphate, bile acid, carbohydrate and lipid metabolism and thereby affect liver homeostasis (Itoh, 2010;Itoh et al, 2016;Kuro-o, 2019).…”

Section: Fibroblast Growth Factor Signalingmentioning

confidence: 99%

Novel Therapeutic Targets in Liver Fibrosis

Zhang

Liu

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Liver fibrosis is end-stage liver disease that can be rescued. If irritation continues due to viral infection, schistosomiasis and alcoholism, liver fibrosis can progress to liver cirrhosis and even cancer. The US Food and Drug Administration has not approved any drugs that act directly against liver fibrosis. The only treatments currently available are drugs that eliminate pathogenic factors, which show poor efficacy; and liver transplantation, which is expensive. This highlights the importance of clarifying the mechanism of liver fibrosis and searching for new treatments against it. This review summarizes how parenchymal, nonparenchymal cells, inflammatory cells and various processes (liver fibrosis, hepatic stellate cell activation, cell death and proliferation, deposition of extracellular matrix, cell metabolism, inflammation and epigenetics) contribute to liver fibrosis. We highlight discoveries of novel therapeutic targets, which may provide new insights into potential treatments for liver fibrosis.

show abstract

Role of fibroblast growth factor signalling in hepatic fibrosis

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 47 publications

References 142 publications

Cell atlas of the regenerating human liver after portal vein embolization

Cell atlas of the regenerating human liver after portal vein embolization

Identification of miRNA-target gene regulatory networks in liver fibrosis based on bioinformatics analysis

Novel Therapeutic Targets in Liver Fibrosis

Contact Info

Product

Resources

About