Idiopathic pulmonary fibrosis: Current and future treatment

The Clinical Respiratory Journal, Journal Year: 2022, Volume and Issue: 16(2), P. 84 - 96

Published: Jan. 10, 2022

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma architecture destroyed, compliance lost, gas exchange compromised in this debilitating condition that leads inexorably to respiratory failure death within 3–5 years of diagnosis. This review discusses treatment approaches IPF current use those appear promising for future development. Data Source The data were obtained from the Randomized Controlled Trials scientific studies published English literature. We used search terms related IPF, antifibrotic treatment, transplant, management. Results Etiopathogenesis not fully understood, options are limited. Pathological features include extracellular matrix remodeling, fibroblast activation proliferation, immune dysregulation, cell senescence, presence aberrant basaloid cells. mainstay therapies oral drugs pirfenidone nintedanib, which can improve quality life, attenuate symptoms, slow progression. Unilateral or bilateral transplantation only shown increase life expectancy. Conclusion Clearly, there an unmet need accelerated research into mechanisms so progress be made therapeutics toward goals increasing expectancy, alleviating improving well‐being.

Language: Английский

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Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14959 - 14959

Published: Nov. 29, 2022

Pulmonary fibrosis is a chronic progressive lung disease that steadily leads to architecture disruption and respiratory failure. The development of pulmonary mostly the result previous acute inflammation, caused by wide variety etiological factors, not resolved over time causing deposition fibrotic tissue in lungs. Despite long history study good coverage problem scientific literature, effective therapeutic approaches for treatment are currently lacking. Thus, molecular mechanisms underlying transition from inflammation fibrosis, search new markers promising targets prevent development, remain highly relevant tasks. This review focuses on etiology, pathogenesis, morphological characteristics outcomes as precursor fibrosis; pathomorphological changes lungs during development; known key players signaling pathways mediating well most common vivo models these processes. Moreover, prognostic injury severity approved potential suppressing discussed.

Language: Английский

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Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: July 21, 2022

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Recent studies have identified the key role of crosstalk between dysregulated epithelial cells, mesenchymal, immune, and endothelial cells in IPF. In addition, genetic mutations environmental factors (e.g., smoking) also been associated with development With recent sequencing technology, epigenetics, as an intermediate link gene expression impacts, has reported to be implicated fibrosis. Although etiology IPF unknown, many novel therapeutic targets agents emerged from clinical trials for treatment past years, successful launch pirfenidone nintedanib demonstrated promising future anti-IPF therapy. Therefore, we aimed gain in-depth understanding underlying molecular mechanisms pathogenic IPF, which would helpful diagnosis anti-fibrotic drugs, improving prognosis patients this study, summarized mechanism, perspective multiple cell types, mutations, epigenetic factors.

Language: Английский

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Hot and Cold Fibrosis: The Role of Serum Biomarkers to assess the Immune Mechanisms and ECM-Cell Interactions in Human Fibrosis

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. In fibrosis, an imbalance between collagen synthesis (fibrogenesis) degradation (fibrolysis) results in the deposition fibrillar collagens disrupting structural integrity ECM and, consequently, architecture. associated with wide range chronic diseases, including liver cirrhosis, kidney pulmonary autoimmune diseases. Recently, concept "hot" "cold" fibrosis has emerged, referring immune status within fibrotic tissues nature fibrogenic signaling. Hot active cell infiltration inflammation, while cold auto- paracrine myofibroblast activation, exclusion quiescence. This article aims explore relationship hot role various types their biologically fragments modulating system, how serological biomarkers can help understanding disease-relevant interactions mesenchymal cells tissues. Additionally, we draw lessons from immuno-oncology research solid tumors shed light on potential strategies for treatment highlight advantage having "hot environment" treat enhancing through modulation system.

Language: Английский

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Regional and disease specific human lung extracellular matrix composition

Biomaterials, Journal Year: 2022, Volume and Issue: 293, P. 121960 - 121960

Published: Dec. 24, 2022

Language: Английский

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Nintedanib solid lipid nanoparticles improve oral bioavailability and ameliorate pulmonary fibrosis in vitro and in vivo models

International Journal of Pharmaceutics, Journal Year: 2023, Volume and Issue: 649, P. 123644 - 123644

Published: Nov. 29, 2023

Language: Английский

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Vincamine Ameliorates Epithelial-Mesenchymal Transition in Bleomycin-Induced Pulmonary Fibrosis in Rats; Targeting TGF-β/MAPK/Snai1 Pathway

Molecules, Journal Year: 2023, Volume and Issue: 28(12), P. 4665 - 4665

Published: June 9, 2023

Idiopathic pulmonary fibrosis is a progressive, irreversible lung disease that leads to respiratory failure and death. Vincamine an indole alkaloid obtained from the leaves of Vinca minor acts as vasodilator. The present study aims investigate protective activity vincamine against EMT in bleomycin (BLM)-induced via assessing apoptotic TGF-β1/p38 MAPK/ERK1/2 signaling pathways. In bronchoalveolar lavage fluid, protein content, total cell count, LDH were evaluated. N-cadherin, fibronectin, collagen, SOD, GPX, MDA levels determined tissue using ELISA. Bax, p53, bcl2, TWIST, Snai1, Slug mRNA examined qRT-PCR. Western blotting was used assess expression TGF-β1, p38 MAPK, ERK1/2, cleaved caspase 3 proteins. H & E Masson's trichrome staining analyze histopathology. BLM-induced fibrosis, reduced activity, differential count. SOD GPX also increased following treatment, while decreased. Additionally, suppressed Snail, genes well factors such p/t proteins, and, at same time, bcl2 gene expression. Moreover, restored N-Catherine, collagen elevation due fibrosis. addition, histopathological examination tissues revealed attenuated fibrotic inflammatory conditions. conclusion, bleomycin-induced by attenuating MAPK/ERK1/2/TWIST/Snai1/Slug/fibronectin/N-cadherin pathway. it exerted anti-apoptotic

Language: Английский

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The role of precision medicine in interstitial lung disease

European Respiratory Journal, Journal Year: 2022, Volume and Issue: 60(3), P. 2102146 - 2102146

Published: Feb. 3, 2022

The management of interstitial lung disease (ILD) may benefit from a conceptual shift. Increased understanding this complex and heterogeneous group disorders over the past 20 years has highlighted need for individualised treatment strategies that encompass diagnostic classification behaviour. Biomarker-based approaches to precision medicine hold greatest promise. Robust, large-scale biomarker-based technologies supporting ILD diagnosis have been developed, future applications relating staging, prognosis assessment response are emerging. Artificial intelligence redefine our ability base prognostic evaluation on both underlying processes, sharpening algorithms level not previously achieved. Compared with therapeutic areas such as oncology, in is still its infancy. However, nature suggests many relevant molecular, environmental behavioural targets serve useful biomarkers if we willing invest their identification validation.

Language: Английский

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Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 438 - 438

Published: March 2, 2024

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

Language: Английский

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It takes two: Aberrant repair and low-grade inflammation characterizes bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Aim The obstructive phenotype of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), is diagnosed after transplantation (LTx) when irreversible airway obstruction already present. This study aimed to investigate the fibrotic response and inflammation signals in serum BOS patients. Methods LTx patients transplanted at University Medical Center Groningen between 2004 2017 were screened. Nineteen with selected matched 19 non-BOS Only for whom function longitudinal samples post-LTx available included. Enzyme-linked immunosorbent assays performed neoepitopes collagen types I, III, VI osteoprotegerin (OPG) serum. Additionally, analyzed by label free liquid chromatography tandem mass spectrometry proteomics analysis. Results Collagen did not differ significantly any timepoint. OPG was higher compared six months before onset (p<0.04). In analysis, proteins indicating cell repair proliferation, namely human type II keratin-6 centromere protein F (both FDR<0.1), lower three C-reactive (FDR<0.05) SERPINA3 amongst others, end-stage Conclusion Differences expression that reflect complex interplay fibrosis identified. These should be investigated validated larger cohorts may aid expanding knowledge about development BOS.

Language: Английский

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