The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: March 25, 2024

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as fibrosis. Alcohol abuse, non-alcoholic fatty disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic injury. Exploring potential therapeutic targets understanding molecular mechanisms involved in fibrosis are essential for development effective interventions. The goal this comprehensive review is explain how PI3K/AKT signaling pathway contributes reduction target investigated through summary results from vivo vitro studies. Studies focusing on activation have shown significant decrease markers improvement function. emphasizes may prevent ECM synthesis hepatic stellate cell (HSC) activation, ultimately reducing fibrotic response. specific downstream effectors constitute rapidly developing field study. In conclusion, plays role attenuating Its complex regulating HSC production, demonstrated both , underscores its approach managing slowing progression. A provides valuable insights into future developments implications clinical applications.

Language: Английский

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Immune Checkpoints and the Immunology of Liver Fibrosis

Livers, Journal Year: 2025, Volume and Issue: 5(1), P. 5 - 5

Published: Jan. 27, 2025

Liver fibrosis is a very complicated dynamic process where several immune cells are involved. Both innate and adaptive immunity implicated, their interplay always present. Multi-directional interactions between liver macrophages, hepatic stellate (HSCs), cells, cytokines important for the induction perpetuation of fibrosis. Detailed studies proteomics transcriptomics have produced new evidence role individual in cirrhosis. Most these controlled by various checkpoints whose main function to maintain homeostasis implicated cells. Recent indicates that involved In particular, programmed cell death protein 1 (PD-1), death-ligand (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) been investigated, particularly after availability checkpoint inhibitors. Their activation leads exhaustion CD4+ve CD8+ve promotion this review, current pathogenesis immunological abnormalities discussed. The recent data on involvement identified as possible targets future interventions.

Language: Английский

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The decrease of selenoprotein K induced by selenium deficiency in diet improves apoptosis and cell progression block in chicken liver via the PTEN/PI3K/AKT pathway

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 189, P. 20 - 31

Published: July 13, 2022

Language: Английский

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SIRT1: Harnessing multiple pathways to hinder NAFLD

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107155 - 107155

Published: March 23, 2024

Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic disorders, with a high prevalence but no approved treatment. Therefore, it indispensable to find trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) strongly associated SIRT1 activation or overexpression attenuate NAFLD, while deficiency aggravates Besides, an array therapeutic agents, including natural compounds, synthetic traditional Chinese medicine formula, stem cell transplantation, alleviates NALFD via upregulation. Mechanically, NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, coordinating lipid metabolism, as well reducing hepatocyte apoptosis inflammation. In this review, we introduced structure function briefly, summarized effect on its mechanism, along application agonists in treating

Language: Английский

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Kinsenoside alleviates inflammation and fibrosis in experimental NASH mice by suppressing the NF-κB/NLRP3 signaling pathway

Phytomedicine, Journal Year: 2022, Volume and Issue: 104, P. 154241 - 154241

Published: June 15, 2022

Language: Английский

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Kinsenoside mitigates myocardial ischemia/reperfusion-induced ferroptosis via activation of the Akt/Nrf2/HO-1 pathway

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 956, P. 175985 - 175985

Published: Aug. 10, 2023

Language: Английский

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PD-1/PD-L1 axis in organ fibrosis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 19, 2023

Fibrosis is a pathological tissue repair activity in which many myofibroblasts are activated and extracellular matrix excessively accumulated, leading to the formation of permanent scars finally organ failure. A variety organs, including lung, liver, kidney, heart, skin, can undergo fibrosis under stimulation various exogenous or endogenous pathogenic factors. At present, pathogenesis still not fully elucidated, but it known that immune system plays key role initiation progression fibrosis. Immune checkpoint molecules regulators maintain tolerance homeostasis, among programmed cell death protein 1/programmed ligand 1 (PD-1/PD-L1) axis has attracted much attention. The exciting achievements tumor immunotherapy targeting PD-1/PD-L1 provide new insights into its use as therapeutic target for other diseases. In recent years, been preliminarily explored, further confirming close relationship signaling, regulation, This review discusses structure, expression, function, regulatory mechanism PD-1 PD-L1, summarizes research progress signaling fibrotic

Language: Английский

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ADORA2B, transcriptionally suppressing by MYC, promotes ferroptosis of chondrocytes via inhibition of the PI3K/Akt pathway in mice with osteoarthritis

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(5), P. 2487 - 2501

Published: Jan. 4, 2024

Abstract Recent studies have shown that chondrocyte ferroptosis contributes importantly to the pathogenesis of osteoarthritis (OA). However, it is largely unknown how regulated. In this study, data sets GSE167852 and GSE190184 were downloaded from Gene Expression Omnibus (GEO) database, 161 differentially expressed genes (DEGs) related screened by bioinformatics analysis. Subsequently, ADORA2B was as a candidate gene DEGs, which significantly upregulated in palmitic acid (PA) treated chondrocytes. CCK‐8, EdU, Western blotting, ferroptosis‐related kits assays demonstrated knockdown constrained promoted viability Overexpression ferroptosis, while PI3K/Akt pathway inhibitor LY294002 reversed promotion on ferroptosis. Dual‐luciferase reporter assay chromatin immunoprecipitation (ChIP) indicated MYC transcription suppressor ADORA2B, overexpression viability, inhibited chondrocytes, abated inhibition vivo experiments showed alleviated cartilage tissue damage OA mice, able overexpression. summary, transcriptionally suppressing MYC, promotes chondrocytes via pathway. Thus, can be used potential treatment target for diseases.

Language: Английский

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Role of glycolysis in inflammatory bowel disease and its associated colorectal cancer

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 10, 2023

Inflammatory bowel disease (IBD) has been referred to as the “green cancer,” and its progression colorectal cancer (CRC) poses a significant challenge for medical community. A common factor in their development is glycolysis, crucial metabolic mechanism of living organisms, which also involved other diseases. In IBD, glycolysis affects gastrointestinal components such intestinal microbiota, mucosal barrier function, immune system, including macrophages, dendritic cells, T neutrophils, while CRC, it linked various pathways, phosphatidylinositol-3-kinase (PI3K)/AKT, AMP-activated protein kinase (AMPK), mammalian target rapamycin (mTOR), transcription factors p53, Hypoxia-inducible (HIF), c-Myc. Thus, comprehensive study essential better understanding pathogenesis therapeutic targets both IBD CRC. This paper reviews role diseases, particularly via effects on immunity, integrity, signaling some strategies targeting glycolytic enzymes.

Language: Английский

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Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 29, 2024

The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing therapeutic results. Targeting is a promising treatment method recent years. importance immune regulation by ultrasound combined with microbubbles now widely recognized. Ultrasound work together to induce antigen release cell through mechanical or thermal effects, promoting presentation T cells’ recognition killing cells, improve immunosuppression microenvironment, which will be breakthrough improving traditional problems such as checkpoint blocking (ICB) himeric receptor (CAR)-T therapy. In order effect TME targeted therapy, it necessary develop optimize application system microbubble for organs diseases. Therefore, combination field continue focus on developing more effective strategies regulate mechanisms, so activate anti-tumor immunity and/or efficacy immune-targeted drugs, At present, potential value therapy has great potential, been confirmed experimental research breast cancer, colon pancreatic prostate provides new alternative idea clinical treatment. This article reviews tumors their microenvironment.

Language: Английский

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