Mechanical force and tensile strain activated hepatic stellate cells and inhibited retinol metabolism

Yi, Suhong; Zhang, Yi; Tang, Dan; Zhu, Liang

doi:10.1007/s10529-015-1785-5

Cited by 19 publications

(10 citation statements)

References 11 publications

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“…Activated HSCs were plated onto collagen-coated BioFlex amino-culture plates (Flexcell International, McKeesport, PA, USA) and grown in DMEM without FBS for 24 h. HSCs were then subjected to a 10% tensile strain, 0.5 Hz for 24 h by using Flexercell FX-2000 system (Flexcell International), as previously described (18). …”

Section: Methodsmentioning

confidence: 99%

Identification of miRNAs associated with the mechanical response of hepatic stellate cells by miRNA microarray analysis

Qin

Luo

et al. 2018

Exp Ther Med

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It has been suggested that hepatic stellate cells (HSCs) could be used in the regulation of liver microcirculation and portal hypertension. The effects of tensile strain on the microRNA (miRNA) profile of HSCs are largely unknown. In this study, we aimed to explore the changes of miRNA expression in tensile strain-treated HSCs. The purity and activation of HSCs were determined by immunofluorescence staining with antibody against desmin and a-SMA, respectively. miRNA profile analysis was performed on HSCs with and without tensile strain treatment (n=3) using microarray analysis. We identified 6 significantly differentially expressed miRNAs (DEMs), including 1 downregulated (rno-miR-125b-2-3p) and 5 upregulated (rno-miR-1224, rho-miR-188-5p, rho-miR-211-3p, rho-miR-3584-5p and rho-miR-466b-5p), which were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) experiments. Further analysis of the DEMs revealed that many important biological processes and signal pathways were triggered in tensile strain-treated HSCs. These include the signal transduction mechanisms associated with protein binding, apoptosis, proliferation, and the FoxO and Wnt signaling pathways. In conclusion, this study presents the specific DEMs in tensile strain-treated HSCs. Our study provide novel miRNA-based information that may enhance our understanding of the pathophysiological processes leading to portal hypertension.

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Section: Methodsmentioning

confidence: 99%

Identification of miRNAs associated with the mechanical response of hepatic stellate cells by miRNA microarray analysis

Qin

Luo

et al. 2018

Exp Ther Med

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“…In this study, we observed the differential expression of multiple phenotype-determining genes upon the restoration of miR-16 expression at 48 h in myofibroblasts. HSC-specific adipogenic genes, including RXRα 32 – 34 , PPARγ 32 – 35 , CEBPα 32 , 36 , 37 , CEBPθ 2 , 32 , Fabp6 2 , 32 , Fabp7 2 , 32 , and Rbp2 38 , 39 , etc., were upregulated with the expression of miR-16. miR-16 also downregulated major fibrosis-inducing cytokines and related genes ( TGFβ2 40 , LTBP4 41 , etc.)…”

Section: Discussionmentioning

confidence: 99%

miR-16 integrates signal pathways in myofibroblasts: determinant of cell fate necessary for fibrosis resolution

Pan

Guo²,

et al. 2020

Cell Death Dis

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Liver fibrosis is characterized by the transdifferentiation of hepatic stellate cells (HSCs) to myofibroblasts and poor response to treatment. This can be attributed to the myofibroblast-specific resistance to phenotype reversal. In this study, we complemented miR-16 into miR-16-deficient myofibroblasts and analyzed the global role of miR-16 using transcriptome profiling and generating a pathway-based action model underlying transcriptomic regulation. Phenotypic analysis of myofibroblasts and fibrogenic characterization were used to understand the effect of miR-16 on phenotypic remodeling of myofibroblasts. miR-16 expression altered the transcriptome of myofibroblasts to resemble that of HSCs. Simultaneous targeting of Smad2 and Wnt3a, etc. by miR-16 integrated signaling pathways of TGF-β and Wnt, etc., which underlay the comprehensive regulation of transcriptome. The synergistic effect of miR-16 on the signaling pathways abolished the phenotypic characteristics of myofibroblasts, including collagen production and inhibition of adipogenesis. In vivo, myofibroblast-specific expression of miR-16 not only eliminated mesenchymal cells with myofibroblast characteristics but also restored the phenotype of HSCs in perisinusoidal space. This phenotypic remodeling resolved liver fibrosis induced by chronic wound healing. Therefore, miR-16 may integrate signaling pathways crucial for the fate determination of myofibroblasts. Its global effect induces the reversal of HSC-tomyofibroblast transdifferentiation and, subsequently, the resolution of fibrogenesis. Taken together, these findings highlight the potential of miR-16 as a promising therapeutic target for liver fibrosis.

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“…It has been reported that such factors regulate cellular proliferation and differentiation. Numerous studies have demonstrated that mechanical force, such as pressure and stretch, is an important regulator in cell metabolism (28–30). The present study suggested that portal hypertension significantly inhibited the synthesis of hepatocellular glycogen.…”

Section: Discussionmentioning

confidence: 99%

Pressure suppresses hepatocellular glycogen synthesis through activating the p53/Pten pathway

et al. 2019

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Portal hypertension is the primary cause of complications in patients with chronic liver diseases, and markedly impacts metabolism within the nervous system. Until recently, the role of portal hypertension in hepatocellular metabolism was unclear. The present study demonstrated that an increase in extracellular pressure significantly decreased hepatocellular glycogen concentrations in HepG2 and HL-7702 cells. In addition, it reduced glycogen synthase activity, by inhibiting the phosphorylation of glycogen synthase 1. RNA-seq analysis revealed that mechanical pressure suppressed glycogen synthesis by activating the p53/phosphatase and tensin homolog pathway, further suppressing glycogen synthase activity. The present study revealed an association between mechanical pressure and hepatocellular glycogen metabolism, and identified the regulatory mechanism of glycogen synthesis under pressure.

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Mechanical force and tensile strain activated hepatic stellate cells and inhibited retinol metabolism

Abstract: Mechanical force and tensile strain significantly activate HSCs by regulating the retinoid metabolic pathway. Activation of HSCs can therefore be manipulated through mechanical force and tensile strain in vitro.

Cited by 19 publications

References 11 publications

Identification of miRNAs associated with the mechanical response of hepatic stellate cells by miRNA microarray analysis

Identification of miRNAs associated with the mechanical response of hepatic stellate cells by miRNA microarray analysis

miR-16 integrates signal pathways in myofibroblasts: determinant of cell fate necessary for fibrosis resolution

Pressure suppresses hepatocellular glycogen synthesis through activating the p53/Pten pathway

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