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

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116116 - 116116

Опубликована: Янв. 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.

Язык: Английский

---

Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Апрель 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

Язык: Английский

---

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

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116295 - 116295

Опубликована: Фев. 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

Язык: Английский

---

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

Biochemical Pharmacology, Год журнала: 2024, Номер 223, С. 116130 - 116130

Опубликована: Март 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.

Язык: Английский

---

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

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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

Язык: Английский

---

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

Journal of Cellular and Molecular Medicine, Год журнала: 2023, Номер 28(2)

Опубликована: Дек. 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.

Язык: Английский

---

Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis

Phytotherapy Research, Год журнала: 2023, Номер 37(11), С. 4932 - 4962

Опубликована: Июль 17, 2023

Abstract Extracellular matrix (ECM) resolution by metalloproteinases (MMPs) is a well‐documented mechanism. MMPs play dual and complex role in modulating ECM degradation at different stages of liver fibrosis, depending on the timing levels their expression. Increased MMP‐1 combats disease progression cleaving fibrillar ECM. Activated hepatic stellate cells (HSCs) increase expression MMP‐2, ‐9, ‐13 chemicals‐induced animal models, which may alleviate or worsen based models stage fibrosis. In early stage, elevated certain damage surrounding tissue activate HSCs, promoting fibrosis progression. At later downregulation can facilitate accumulation A number phytochemicals modulate MMP activity turnover, alleviating However, effects are variable depend dosage, duration used each study. Here, we review most recent advances fibrogenesis, indicates that further studies warranted to confirm define potential clinical efficacy these phytochemicals.

Язык: Английский

---

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

Current Stem Cell Research & Therapy, Год журнала: 2024, Номер 19(11), С. 1484 - 1496

Опубликована: Янв. 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.

Язык: Английский

---

Recent advances of nanomaterials in imaging liver fibrosis

BMEMat, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Abstract Liver fibrosis is a pathological process resulting from prolonged exposure to various injury factors. It characterized by the abnormal proliferation and activation of hepatic stellate cells excessive deposition extracellular matrix. If left untreated, it can progress cirrhosis, liver failure, even cancer. There currently no efficient accurate clinical diagnostic method for early fibrosis. Therefore, there an urgent need address challenge staging diagnosis in practice. Recently, nanomaterials have demonstrated significant potential enhancing Nanomaterials possess ability precisely identify target microenvironment associated with By their enrichment area, improve imaging contrast lesions liver, thereby enabling Accordingly, this review delves into latest research advancements concerning diagnosis.

Язык: Английский

---

Hepatic stellate cell-targeted chemo-gene therapy for liver fibrosis using fluorinated peptide-lipid hybrid nanoparticles

Journal of Controlled Release, Год журнала: 2024, Номер 376, С. 601 - 617

Опубликована: Окт. 25, 2024

Язык: Английский

---