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

Wang, Yuling; Jiao, Linke; Qiang, Caoxia; Chen, Chen; Shen, Zihuan; Ding, Fan; Lv, Lifei; Zhu, Tingting; Lu, Yingdong; Cui, Xiangning

doi:10.1016/j.biopha.2023.116116

Cited by 13 publications

(3 citation statements)

References 170 publications

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“…The differential effect of both compounds on protein secretion and gene expression of MMP-9 at given time can be related to negative feedback regulation. Importantly MMP-9 synthesis has been shown to be regulated by several mechanisms, including gene expression, post-transcriptional processing and post-translational level 52 . Dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) has been shown to down-regulate MMP-9 mRNA expression in macrophages treated with cannabinoid agonist R( +) WIN55,212–2.…”

Section: Discussionmentioning

confidence: 99%

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model

Kostadinova,

Ströbel,

Chen

et al. 2024

Sci Rep

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Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-β antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.

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Section: Discussionmentioning

confidence: 99%

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model

Kostadinova,

Ströbel,

Chen

et al. 2024

Sci Rep

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Section: Potential Targets For the Molecular Imaging Of Rheumatoid Ar...mentioning

confidence: 99%

“…MMPs are produced by macrophages, endothelial cells, leukocytes, synoviocytes, and chondrocytes and are essential for developmental and repair processes. Inflammatory cytokines stimulate the synthesis of MMPs (Figure 19) [173,174]. The most significant MMPs in RA are MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13, which cleave fibrillar collagen and are correlated with VEGF and uPA.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m

Ali,

Benfante,

Di Raimondo

et al. 2024

Life

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Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA.

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Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets

Nisar,

Khan,

et al. 2024

MedComm

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Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age‐related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia‐targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia‐induced pathways to enhance healthy aging and reduce the burden of age‐related diseases.

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

Cited by 13 publications

References 170 publications

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model

A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m

Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets

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