Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling through GFAP-ACTA2 protein interaction in liver fibrosis

Hassan, Sobia; Zil-e-Rubab,; Hussain, Sayed; Shawana, Summayya

doi:10.12669/pjms.36.4.1845

Cited by 5 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…What is more, the ACTA2 has been indicated to be associated with hepatitis C virus-induced hepatic fibrosis. 38 Here, we also reported an upregulated expression level of ACTA2, which is consistent with a previous study. However, due to the relatively small number of clinical samples available in this study, and the complex mechanism of liver cirrhosis, further studies and large sample studies, incorporating clinical information, are required to validate the functions of these genes in liver cirrhosis or HCC progress.…”

Section: Discussionsupporting

confidence: 93%

Unraveling the activation process and core driver genes of HSCs during cirrhosis by single-cell transcriptome

Li,

Wang,

et al. 2023

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Worldwide, cirrhosis is a common cause of death, manifesting itself as fibrosis of the liver tissue. When the liver is damaged, the liver produces fibrotic, proliferative myofibroblasts, which are formed by the differentiation of activated hepatic stellate cells. There are no effective antifibrotic treatment options. To deeply explore the activation process of hepatic stellate cells (HSCs) and to discover better therapeutic target genes, single-cell RNA sequencing data on 13 non-cirrhotic liver tissue samples and 10 cirrhotic liver tissue samples were analyzed. We identified activated HSCs from the mesenchymal cell population with high expression of ACTA2. By pseudo-time analysis, we found that the key genes for the differentiation of HSCs into myofibroblasts were C3, CCDC80, COL1A1, COL3A1, DCN, FBLN1, IGFBP3, MXRA5, SERPINE1, and MYH11. Then, we found that the main regulators of HSCs from inactive to activated state were NTF3, NTRK3, NTRK2, JAG1, NOTCH3, ESAM, and CD46 by cell–cell communication analysis. In addition, we found that the top2 hub genes of activated HSCs were CRIP1 and ACTA2. The experimental results show that the top2 hub genes were significantly overexpressed in cirrhotic samples. Our work dissected key intercellular regulators and core driver genes during hepatic stellate cell activation during cirrhosis through single-cell transcriptome data analysis, providing a research strategy to discover rational therapeutic targets for cirrhosis and some important information for gene targeting therapy.

show abstract

Section: Discussionsupporting

confidence: 93%

Unraveling the activation process and core driver genes of HSCs during cirrhosis by single-cell transcriptome

Li,

Wang,

et al. 2023

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…[30,31] PRKCA has also been reported to be involved in the brosis process of liver, kidney and other organs. [16,17] Our results showed that PRKCA is the target gene of miR-647, participate in miR-647 regulated process of atrial brosis, indicating that PRKCA is an important gene in the pathogenesis of AF.…”

Section: Discussionmentioning

confidence: 65%

“…Recent researches discovered that up-regulation of PRKCA could increase the brosis of renal and liver. [16,17] Additionally, PRKCA increases the vulnerability to AF by dysregulation of calcium signaling, suggesting that PRKCA may be involved in the occurrence and maintenance of AF. [18] In our previous studies, bioinformatics analysis was used to analyze the differentially expressed genes in atrial tissues of sinus rate (SR) and AF patients.…”

Section: Introductionmentioning

confidence: 99%

MiR-647 Targeting PRKCA to Regulate the Activation of Human Atrial Fibroblasts Through TGFβ1/Smad Pathway

Yan

Han

Tian

2022

Preprint

View full text Add to dashboard Cite

Background Atrial remodeling is the main pathogenesis of atrial fibrillation (AF). Interstitial fibrosis is an important part of atrial remodeling, mainly involving the activation of atrial fibroblasts. Nowadays, studies have focused on miRNAs in regulating fibroblasts in AF related atrial fibrosis, however, the molecular mechanism of this pathological process is not fully understood. Methods Cell experiments were carried out to investigate the mechanism of miR-647 targeting PRKCA gene in regulating atrial fibrosis of AF. CCK-8, transwell, immunofluorescence assays were applied to observe the proliferation, migration and the phenotypic transformation of the human atrial fibroblasts. qRT-PCR and WB were used to detect the collagen production, expression levels of α-SMA and TGFβ1/Smad pathway. Results The results of CCK-8, transwell and immunofluorescence assays showed that miR-647 inhibited the proliferation, migration and the fluorescence intensity of α-SMA of the human atrial fibroblasts. QRT-PCR and WB showed that miR-647 could significantly attenuate the expression levels of fibrosis related Collagen I and III, α-SMA and TGFβ1/Smad pathway by targeting PRKCA. Conclusion MiR-647 targeting PRKCA gene regulates the activation of human atrial fibroblasts through the TGFβ1/Smad pathway.

show abstract

“…Activation of HSCs and their transformation to myofibroblasts is an example of that one. Moreover, another example of cell transformation caused by TGF-β is EMT in hepatocytes accompanied with loss of cell-cell contacts and polarity [50]. Actually, TGF-β stimulates almost of all liver cell populations (portal and resident fibroblasts, bone marrow-derived fibrocytes, endothelial cells, vascular smooth muscle cells, pericytes and cholangiocytes additionally to hepatocytes and HSCs) to change into a more fibroblastic phenotype [40] and to release profibrogenic transcriptional program manifested by upregulation of collagen expression [41] and disturbances in ECM turnover through imbalance between MMPs and TIMPs.…”

Section: Tgfβrmentioning

confidence: 99%

Therapy that Targets Growth Factor Receptors: Novel Approach for Liver Cirrhosis Treatment

Kuznietsova¹,

Ogloblya²

2021

Advances in Hepatology

View full text Add to dashboard Cite

The background of liver fibrous degeneration is excessive cell proliferation including hepatic stellate cells, inflammatory cells, fibroblasts and myofibroblasts. Often it is the consequence of increased growth factors and/or their receptors expression. Key contributors to the liver cell proliferation are EGFR, FGFR, PDGFR, VEGFR, TGFβR, the increased expression of which is indicated on in vitro and in vivo models of liver fibrosis and in patients who experienced fibrosis-accompanied liver diseases. Elimination of growth factors/suppression of their receptors is associated with the weakening/elimination of certain processes responsible for fibrogenesis. This chapter represents the evidences of the efficacy of growth factor receptors signaling downregulation for the suppression of liver fibrosis and cirrhosis and their individual manifestations. The data on established and experimental therapeutics – specific and multikinase growth factor receptor inhibitors which demonstrated antifibrotic and anticirrhotic activity under in vitro and in vivo models, are also presented.

show abstract

Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling through GFAP-ACTA2 protein interaction in liver fibrosis

Cited by 5 publications

References 23 publications

Unraveling the activation process and core driver genes of HSCs during cirrhosis by single-cell transcriptome

Unraveling the activation process and core driver genes of HSCs during cirrhosis by single-cell transcriptome

MiR-647 Targeting PRKCA to Regulate the Activation of Human Atrial Fibroblasts Through TGFβ1/Smad Pathway

Therapy that Targets Growth Factor Receptors: Novel Approach for Liver Cirrhosis Treatment

Contact Info

Product

Resources

About