The role of matrix metalloproteinase 9 in fibrosis diseases and its molecular mechanisms

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116116 - 116116

Published: Jan. 5, 2024

Fibrosis is a process of tissue repair that results in the slow creation scar to replace healthy and can affect any or organ. Its primary feature massive deposition extracellular matrix (mainly collagen), eventually leading dysfunction organ failure. The progression fibrotic diseases has put significant strain on global health economy, as result, there an urgent need find some new therapies. Previous studies have identified inflammation, oxidative stress, cytokines, remodeling play crucial role are essential avenues for treating diseases. Among them, metalloproteinases (MMPs) considered main targets treatment since they driver involved ECM degradation, inhibitors (TIMPs) natural endogenous MMPs. Through previous studies, we found MMP-9 target However, it worth noting plays bidirectional regulatory different stages same disease. Previously inhibitors, such pirfenidone nintedanib, suffer from rather pronounced side effects, therefore, investigate drugs. In this review, explore mechanism action signaling pathways tissues organs, hoping provide ideas developing safer more effective biologics.

Language: Английский

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Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: April 20, 2023

Chronic liver disease or repeated damage to hepatocytes can give rise hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the parenchyma. Changes composition ECM lead stiffness that destroys its inherent mechanical homeostasis, homeostasis imbalance activates stellate cells (HSCs) into myofibroblasts, which overproliferate secrete large amounts proteins. Excessive are gradually deposited Disse gap, regeneration fails, further leads changes components an increase stiffness, forming vicious cycle. These processes promote occurrence development In this review, dynamic remodeling HF activation HSCs mechanotransduction signaling pathways for myofibroblasts participate discussed. may have potential therapeutic targets repairing reversing

Language: Английский

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Research progress on the pharmacological mechanism, in vivo metabolism and structural modification of Erianin

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116295 - 116295

Published: Feb. 23, 2024

Erianin is an important bibenzyl compound in dendrobium and has a wide spectrum of pharmacological properties. Since was discovered, abundant results have been achieved the vitro synthesis, structural modification, mechanism research. Researchers developed series simple efficient synthesis methods to improve shortcomings poor water solubility by replacing chemical structure or coating it nanomaterials. broad anti-tumor significant effects. In addition, also actions like immune regulation, anti-inflammatory, anti-angiogenesis. A comprehensive understanding metabolism, action pathways great value for utilization Erianin. Therefore, this review conducts relatively systematic look back at from above four aspects, give reference evolvement further appliance

Language: Английский

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hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 5, 2025

Pulmonary fibrosis (PF) is a common and multidimensional devastating interstitial lung disease. The development of novel more effective interventions for PF an urgent clinical need. A previous study has found that miR-181a-5p plays important role in the PF, human amniotic mesenchymal stem cells (hAMSCs) exert potent therapeutic potential on PF. However, whether hAMSCs act by delivering its detailed mechanism still remain unknown. Thus, this was designed to investigate underlying possible bleomycin (BLM)-induced mouse model, co-culture system A549 epithelial transition (EMT) focusing effects collagen deposition, EMT, cell cycle regulation. with different expression levels were constructed. BLM (4 mg/kg) used create while TGF-β1 induce construct EMT model. Furthermore, deposition during assessed vivo vitro. We exerted anti-fibrotic effect BLM-induced Moreover, also protective TGFβ1-induced ameliorated promoting proliferation, reducing apoptosis, attenuating through paracrine effects. regulated targeting TGFBR1. Our findings reveal first time inhibit EMT. Mechanistically, hMASCs achieved

Language: Английский

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Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 28(2)

Published: Dec. 2, 2023

Abstract Fibrosis refers to excessive build‐up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that cytokines chemokines, especially Transforming growth factor beta (TGF‐β) is involved the pathogenesis fibrosis. It shown TGF‐β upregulated fibrotic tissues, contributes fibrosis by mediating pathways are related preservation fibroblasts differentiation. There no doubt antioxidants protect against inflammatory conditions reversing effects nitrogen, oxygen sulfur‐based reactive elements. Oxidative stress a direct impact on chronic inflammation, as results, prolonged inflammation ultimately results Different types antioxidants, forms vitamins, natural compounds or synthetic ones, have proven be beneficial protection both vitro vivo. this study, we reviewed role with antioxidant activity induction inhibition TGF‐β/SMAD signalling pathway, regard such gastro‐intestinal fibrosis, cardiac pulmonary skin renal also some rare cases animal models cell lines.

Language: Английский

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The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 223, P. 116130 - 116130

Published: March 13, 2024

Organ scarring, referred to as fibrosis, results from a failed wound-healing response chronic tissue injury and is characterised by the aberrant accumulation of various extracellular matrix (ECM) components. Once established, fibrosis recognised hallmark stiffened dysfunctional tissues, hence, fibrosis-related diseases collectively contribute high morbidity mortality in developed countries. Despite this, these are ineffectively treated currently-available medications. The pro-fibrotic cytokine, transforming growth factor (TGF)-β1, has emerged master regulator progression, owing its ability promote factors processes that facilitate rapid ECM synthesis deposition, whilst negating degradation. Whilst TGF-β1 signal transduction tightly controlled canonical (Smad-dependent) non-canonical (MAP kinase- Rho-associated protein kinase-dependent) intracellular activity, actions can also be facilitated Wnt/β-catenin pathway. This review outlines pathological sequence events contributing role progression how pathway contributes repair acute disease settings, but related dysfunction synergy with diseases. It anti-fibrotic mechanisms hormone, relaxin, mediated via negative modulation signaling, through promotion activity settings. Collectively, this highlights crosstalk between cascade may provide therapeutic target exploited broadly treat reverse established fibrosis.

Language: Английский

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Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver

Current Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 19(11), P. 1484 - 1496

Published: Jan. 11, 2024

The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy also proposed as a promising strategy for fibrosis treatment. Recent studies have shown that the co-administration MSCs drugs demonstrates pronounced effect on fibrosis.

Language: Английский

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The Novel Effect and Potential Mechanism of Lactoferrin on Organ Fibrosis Prevention

Nutrients, Journal Year: 2025, Volume and Issue: 17(1), P. 197 - 197

Published: Jan. 6, 2025

Organ fibrosis is gradually becoming a human health and safety problem, various organs of the body are likely to develop fibrosis. The ultimate pathological feature numerous chronic diseases fibrosis, few interventions currently available specifically target pathogenesis medical detection organ has matured. However, there no effective treatment method for these diseases. Therefore, we need strive developing reliable drugs or substances treat prevent fibrotic Lactoferrin (LF) multifunctional glycoprotein with many physiologically active effects, such as antioxidant, anti-inflammatory antimicrobial it protects against physiological conditions in disease models. This review summarizes effects underlying mechanisms LF preventing As naturally substance, can be used promising drug prevention remission

Language: Английский

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A Single-Chain Peptide Probe Targeting Pathological Collagen for Precise Staging of Hepatic Fibrosis by MR Imaging

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and cancer, necessitates urgent noninvasive diagnostic techniques halt disease progression. We herein for the first time developed single-chain peptide probe targeting pathological collagen in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)10 probe, distinguished by its unique monomeric conformation achieved through Pro (2S,4S)-hydroxyproline (hyp) substitution subsequent disruption hydrogen bonding, exhibits selectivity over intact counterpart connective tissues. Fluorescence specimens from fibrotic models displayed discernible relationship between levels fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent severity, corroborated corresponding increase contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that has low Gd retention main organs 24 h postinjection, ensuring probe's safety molecular imaging. therefore emerges as potent tool precise, delineation stages, offering significant implications diagnosis management

Language: Английский

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A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract Objective This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy. Methods randomized controlled included 50 HCV-infected with fibrosis stage (F1 & F2). Participants were randomly assigned two groups: Group 1 (Control group, n = 25) received standard therapy for 3 months, while 2 (Zinc mg/day addition same duration. Baseline and 3-month post-intervention assessments evaluating serum levels hyaluronic acid, transforming growth factor beta-1, fibronectin. Furthermore, indices liver fibrosis, such as Fibrosis Index based on 4 factors (FIB-4) Aspartate Transaminase-to-Platelet-Ratio (APRI), calculated during these assessments. Results At baseline, studied groups had no statistical difference demographic laboratory data. After treatment, significantly increased zinc-treated group compared control group. Additionally, fibronectin acid reduced (zinc group) (control group). Moreover, showed lower APRI scores than after a follow-up period, but there was non-significant FIB-4 between treatment. total bilirubin months. Conclusions Administering could potentially serve safe efficient therapeutic strategy management hepatic individuals hepatitis virus. Trial Registration ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Language: Английский

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