Unraveling the Exosome-miR-133a Axis: Targeting TGF-β Signaling via WJ-MSC-Derived Exosomes for Anti-Fibrotic Therapy in Liver Fibrosis DOI Creative Commons

Sahar Saki,

Sajad Monjezi,

Fatemeh Ghaffari

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 28(5), P. 235 - 244

Published: Sept. 1, 2024

One of the primary drivers liver fibrosis is excessive accumulation extracellular matrix (ECM), primarily caused by over-proliferation hepatic star-shaped cells (HSCs). The activation HSCs transforming growth factor beta (TGF-β) has a critical role in initiating fibrosis. Recent studies have suggested that miRNA-133a significantly regulates fibrogenesis process, which its downregulation associated with progression. Understanding provides potential therapeutic insights for targeting TGF-β signaling and mitigating We investigated whether exosomes could attenuate enhancing antifibrotic effects miR-133a. LX-2 cell line was treated 24 hours, followed an additional hours treatment exosomes. After this period, we assessed mRNA expression levels α-SMA, collagen 1, miR-133a, as well protein p-Smad3. exposure increased level α-SMA 1 genes elevated p-Smad3 protein. Additionally, it resulted significant miR-133a compared to control group. Exosome administration effectively reduced TGF-β-induced upregulation p-Smad3, genes, but levels. Our findings indicate partially can inhibit persistent HSCs. Furthermore, context vitro fibrosis, suppress TGF-β/Smad3 pathway, reducing ECM.

Language: Английский

From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease DOI Creative Commons

Mi Zhou,

Jianyu Lv, Han Y. H. Chen

et al.

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101777 - 101777

Published: Jan. 1, 2025

Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, other components of the syndrome. As our comprehension MASLD deepens, it has become evident that this condition extends beyond liver, embodying complex, multi-systemic with hepatic manifestations mirror broader landscape. This comprehensive review delves into critical interplay between gut-liver axis oxidative stress, elucidating their pivotal roles in etiology progression MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger stress through enhanced ROS production hepatocytes Kupffer cells, leading mitochondrial dysfunction lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation endotoxins like LPS, which activate inflammatory pathways TLR4 signaling promote via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB Nrf2 serve crucial mediators axis, regulating responses orchestrating antioxidant defenses; (4) Oxidative stress-induced damage function creates destructive feedback loop, further exacerbating inflammation progression. These findings highlight complex interrelationship pathogenesis, suggesting potential therapeutic targets for management.

Language: Английский

Citations

1
Immune Checkpoints and the Immunology of Liver Fibrosis DOI Creative Commons
Ioannis Tsomidis, Argyro Voumvouraki, Elias Kouroumalis

et al.

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

Citations

1
Utilizing Nanoparticles of Hesperidin Loaded on Layered Double Hydroxide to Reduce Hepatotoxicity Caused by Paracetamol in Rats: Controlling of Biotransformation, Oxidative Stress, Inflammation, and Apoptosis DOI Creative Commons

Deyaa A. Shaban,

Ahmed A. G. El‐Shahawy,

Mohamed I. Zanaty

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 429 - 429

Published: March 27, 2025

Background/Objectives: The most used antipyretic and pain relief treatment is paracetamol (acetaminophen), also known as N-acetyl-para-aminophenol (APAP). However, it considered potentially hazardous if consumed repeatedly in large doses or over prolonged periods. This investigation explores the effectiveness of hesperidin (Hesp) Hesp loaded on layered double hydroxide nanoparticles (Hesp-NPs) inhibiting progression acute hepatotoxicity rats induced by APAP. Methods: LDH-Hesp-NPs were prepared characterized. Male Wistar orally treated with Hesp-NPs at same adjusted dose (100 mg/kg) every other day for six weeks. After 2 h first Hesp-NPs, received one oral APAP (750 mg/kg). Results: Administering to APAP-treated significantly reduced oxidant parameter (malondialdehyde) serum enzymes (ALT, AST, LDH, ALP) associated liver function. Antioxidant markers liver, such catalase glutathione, increased notably. Moreover, enhanced mRNA expression UGT1A6, IL-10, HO-1. Conversely, expressions CYP1A1, KEAP1, TGF-β, P53, BAX decreased. These improvements biochemical molecular corroborated histopathology. Conclusions: protect against APAP-induced male rats. was more potent. protective effects may be mediated via modulation biotransformation, oxidative stress, inflammation apoptosis.

Language: Английский

Citations

0
Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression DOI Creative Commons
Roohi Chaudhary, Ralf Weiskirchen, Marcelo Ehrlich

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

The transforming growth factor-β (TGF-β) superfamily (TGF-β-SF) comprises over 30 cytokines, including TGF-β, activins/inhibins, bone morphogenetic proteins (BMPs), and differentiation factors (GDFs). These cytokines play critical roles in liver function disease progression. Here, we discuss Smad-dependent (canonical) non-Smad pathways activated by these a hepatocellular context. We highlight the connection between deregulation of or balance them key processes (e.g., proliferation, apoptosis, epithelial-mesenchymal transition (EMT)). further their contribution to various chronic conditions, such as metabolic dysfunction-associated steatotic (MASLD), steatohepatitis (MASH), carcinoma (HCC). In MASLD MASH, TGF-β signaling contributes hepatocyte lipid accumulation, cell death fibrosis progression through both Smad pathways. HCC, other TGF-β-SF have dual role, acting tumor suppressors promoters early vs. advanced stages progression, respectively. Additionally, review involvement modulating responses particularly context diseases, well interdependence with (cholesterol metabolism, insulin resistance, oxidative stress lipotoxicity) MASLD/MASH pathogenesis. perspectives insights detailed this may assist determining future research directions therapeutic targets diseases cancer.

Language: Английский

Citations

0
Unraveling the Exosome-miR-133a Axis: Targeting TGF-β Signaling via WJ-MSC-Derived Exosomes for Anti-Fibrotic Therapy in Liver Fibrosis DOI Creative Commons

Sahar Saki,

Sajad Monjezi,

Fatemeh Ghaffari

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 28(5), P. 235 - 244

Published: Sept. 1, 2024

One of the primary drivers liver fibrosis is excessive accumulation extracellular matrix (ECM), primarily caused by over-proliferation hepatic star-shaped cells (HSCs). The activation HSCs transforming growth factor beta (TGF-β) has a critical role in initiating fibrosis. Recent studies have suggested that miRNA-133a significantly regulates fibrogenesis process, which its downregulation associated with progression. Understanding provides potential therapeutic insights for targeting TGF-β signaling and mitigating We investigated whether exosomes could attenuate enhancing antifibrotic effects miR-133a. LX-2 cell line was treated 24 hours, followed an additional hours treatment exosomes. After this period, we assessed mRNA expression levels α-SMA, collagen 1, miR-133a, as well protein p-Smad3. exposure increased level α-SMA 1 genes elevated p-Smad3 protein. Additionally, it resulted significant miR-133a compared to control group. Exosome administration effectively reduced TGF-β-induced upregulation p-Smad3, genes, but levels. Our findings indicate partially can inhibit persistent HSCs. Furthermore, context vitro fibrosis, suppress TGF-β/Smad3 pathway, reducing ECM.

Language: Английский

Citations

0