Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies

Lurje, Isabella; Gaisa, Nadine T.; Weiskirchen, Ralf; Tacke, Frank

doi:10.1016/j.mam.2023.101191

Cited by 40 publications

(29 citation statements)

References 182 publications

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“…1.3.1 | TGFβ: a downstream protein of CTGF TGFβ plays a crucial role in the pathogenesis of pulmonary fibrosis by activating fibroblasts and stimulating ECM production. 27 Alveolar macrophages are prompted to release substances such as CC chemokine ligand 2 (CCL2), 28 oxidized phospholipids, 29,30 and citrullinated vimentin (Cit-Vim), 31 which enhance the expression of TGFβ and CTGF, exacerbating pulmonary fibrosis. TGFβ also promotes fibroblast proliferation, stimulates granulation tissue formation and collagen deposition.…”

Section: F I G U R Ementioning

confidence: 99%

Drugs targeting CTGF in the treatment of pulmonary fibrosis

Qiu,

Que,

Ding

et al. 2024

J Cellular Molecular Medi

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Pulmonary fibrosis represents the final alteration seen in a wide variety of lung disorders characterized by increased fibroblast activity and the accumulation of substantial amounts of extracellular matrix, along with inflammatory damage and the breakdown of tissue architecture. This condition is marked by a significant mortality rate and a lack of effective treatments. The depositing of an excessive quantity of extracellular matrix protein follows the damage to lung capillaries and alveolar epithelial cells, leading to pulmonary fibrosis and irreversible damage to lung function. It has been proposed that the connective tissue growth factor (CTGF) plays a critical role in the advancement of pulmonary fibrosis by enhancing the accumulation of the extracellular matrix and exacerbating fibrosis. In this context, the significance of CTGF in pulmonary fibrosis is examined, and a summary of the development of drugs targeting CTGF for the treatment of pulmonary fibrosis is provided.

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Section: F I G U R Ementioning

confidence: 99%

Drugs targeting CTGF in the treatment of pulmonary fibrosis

Qiu,

Que,

Ding

et al. 2024

J Cellular Molecular Medi

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“…However, a plethora of other NPCs (e.g., liver-resident macrophages) contribute to fibrogenesis in the liver. A comprehensive review of the underlying mechanisms and involved cell types was recently published [39].…”

Section: Viral Hepatitismentioning

confidence: 99%

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

Kaps,

Limeres,

Schneider

et al. 2023

IJMS

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Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases.

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“…Fibrosis, or tissue “scarring”, is a complex, often lethal disease process driven by different cell types and affecting multiple vital organs [ 1 , 2 , 3 , 4 , 5 ]. Even though fibrosis contributes to up to 45% of deaths in industrialized areas, there remains a limited understanding of how fibrosis develops over time and how the process could be reversed and resolved [ 2 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Lloyd,

2024

Cells

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The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications to ECM proteins such as collagens alter ECM structure and function. Dysregulation of crosslinking enzymes as well as changes in crosslinking composition are prevalent in fibrosis. Because of the crucial roles these ECM crosslinking pathways play in disease, the enzymes that govern crosslinking events are being explored as therapeutic targets for fibrosis. Here, we review in depth the molecular mechanisms underlying ECM crosslinking, how ECM crosslinking contributes to fibrosis, and the therapeutic strategies being explored to target ECM crosslinking in fibrosis to restore normal tissue structure and function.

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Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies

Cited by 40 publications

References 182 publications

Drugs targeting CTGF in the treatment of pulmonary fibrosis

Drugs targeting CTGF in the treatment of pulmonary fibrosis

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

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