Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis DOI
Paolo Spagnolo, Roberto Tonelli, Marco Mura

et al.

Expert Opinion on Investigational Drugs, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: Feb. 7, 2025

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown cause that occurs primarily in older adults and associated with poor quality life substantial healthcare utilization. IPF has dismal prognosis. Indeed, first-line therapy, which includes nintedanib pirfenidone, does not stop progression often tolerability issues. Therefore, there remains high medical need for more efficacious better tolerated treatments. Gene therapy relatively unexplored field research the potential to mitigate range profibrotic pathways by introducing genetic material into cells. Here, we summarize critically discuss publications have explored safety efficacy gene experimentally-induced animals, as clinical studies humans been published yet. The application requires further investigation address several technical biological hurdles, improve vectors' design, drug delivery, target selection, off-target effects develop markers penetration Long-term data are needed bring one step closer practice.

Language: Английский

Activated fibroblasts in cancer: Perspectives and challenges DOI Creative Commons
Giuseppina Caligiuri, David A. Tuveson

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 434 - 449

Published: March 1, 2023

Language: Английский

Citations

170
Pulmonary fibrosis: from pathogenesis to clinical decision-making DOI
Thomas Koudstaal, Manuela Funke-Chambour, Michael Kreuter

et al.

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(12), P. 1076 - 1087

Published: Sept. 15, 2023

Language: Английский

Citations

76
Fibroblasts in Diabetic Foot Ulcers DOI Open Access
Francesca Voza, Carlos Theodore Huerta, Nga Le

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2172 - 2172

Published: Feb. 11, 2024

Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These were previously considered to be “passive cells”, solely responsible for ensuring turnover extracellular matrix (ECM). However, their versatility, including ability switch phenotypes response tissue injury and dynamic activity maintenance specific homeostasis integrity have been recently revealed by innovation technological tools such as genetically modified mouse models single cell analysis. highly plastic heterogeneous equipped with multifaceted functions regulation angiogenesis, inflammation well innate stemness characteristics, play a central role delicately regulated process wound healing. Fibroblast dysregulation underlies many chronic conditions, cardiovascular diseases, cancer, inflammatory diabetes mellitus (DM), which represent current major causes morbidity mortality worldwide. Diabetic foot ulcer (DFU), one most severe complications DM affects 40 60 million people. Chronic non-healing DFU wounds expose patients substantial sequelae infections, gangrene, amputation, death. A complete understanding pathophysiology targeting pathways involved fibroblasts required development innovative new therapeutic treatments, critically needed these patients.

Language: Английский

Citations

17
Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis DOI
Natalia Alkon, Frank P. Assen,

T. Arnoldner

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(2), P. 420 - 435

Published: May 18, 2023

Language: Английский

Citations

36
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy DOI Creative Commons
Farhad Bazgir,

Julia Nau,

Saeideh Nakhaei‐Rad

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1780 - 1780

Published: July 4, 2023

Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to arrhythmia sudden death. While physiological adaptive, resulting from conditions comprising hypertension, aortic stenosis, or genetic mutations, such as hypertrophic cardiomyopathy, maladaptive. Here, we highlight essential role reciprocal interactions involving both cardiomyocytes non-myocardial cells in response pathological conditions. Prolonged cardiovascular stress causes enter an activated state releasing numerous pro-hypertrophic, pro-fibrotic, pro-inflammatory mediators vasoactive hormones, growth factors, cytokines, i.e., commencing signaling events that collectively cause hypertrophy. Fibrotic remodeling mediated by fibroblasts central players, but also endothelial resident infiltrating immune enhance these processes. Many are now being integrated into computational models provide system-level insights will help translate our knowledge new pharmacological targets. This perspective article summarizes last decades' advances research discusses herein-involved complex myocardial microenvironment components.

Language: Английский

Citations

32
Idiopathic pulmonary fibrosis DOI Creative Commons
Thomas Koudstaal, Marlies Wijsenbeek

La Presse Médicale, Journal Year: 2023, Volume and Issue: 52(3), P. 104166 - 104166

Published: May 6, 2023

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It associated cough, dyspnea and impaired quality of life. If left untreated, IPF has median survival 3 years. affects ∼3 million people worldwide, increasing incidence in older patients. The current concept pathogenesis that results from repetitive injury to the epithelium, fibroblast accumulation, myofibroblast activation, deposition matrix. These injuries, combination innate adaptive immune responses, dysregulated wound repair dysfunction, lead recurring tissue remodeling self-perpetuating as seen IPF. diagnostic approach includes exclusion other interstitial diseases or underlying conditions depends on multidisciplinary team-based discussion combining radiological clinical features well some cases histology. In last decade, considerable progress been made understanding management, availability two drugs, pirfenidone nintedanib, decrease function decline. However, therapies only slow progression prognosis remains poor. Fortunately, there are multiple trials ongoing potential new targeting different pathways. This review provides an overview epidemiology, insights pathophysiology, therapeutic management approaches. Finally, detailed description evolving approaches also provided.

Language: Английский

Citations

31
Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer DOI Creative Commons
Nataliya Basalova,

Arbatskiy Mikhail,

Попов Владимир

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1399 - 1412

Published: July 3, 2023

Abstract To date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent development and facilitate resolution. Surprisingly, intratracheal application extracellular vesicles (MSC-EVs) or vesicle-depleted fraction (MSC-SF) was not able lung when applied immediately after injury caused by bleomycin instillation in mice. However, MSC-EV administration induced resolution established fibrosis, whereas did not. The MSC-EVs a decrease numbers myofibroblasts FAPa + progenitors without affecting their apoptosis. Such likely occurred due dedifferentiation microRNA (miR) transfer MSC-EVs. Using murine model bleomycin-induced confirmed contribution specific miRs (miR-29c miR-129) antifibrotic effect Our study provides novel insights into possible therapy based on use vesicle-enriched MSC secretome.

Language: Английский

Citations

24
Extracellular vesicles associated microRNAs: Their biology and clinical significance as biomarkers in gastrointestinal cancers DOI
Yuan Li,

Silei Sui,

Ajay Goel

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 99, P. 5 - 23

Published: Feb. 1, 2024

Language: Английский

Citations

12
MAP kinase phosphatase-1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution DOI Creative Commons

Sean M. Fortier,

Natalie Walker, Loka R. Penke

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(10)

Published: March 21, 2024

Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosis-resistant myofibroblasts (MFs), which arise primarily differentiation resident fibroblasts. Endogenous molecular brakes that promote MF dedifferentiation clearance during spontaneous resolution experimental lung fibrosis may provide insights could inform improve treatment progressive pulmonary in patients. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) influences cellular phenotype fate through precise timely regulation MAPK activity within various cell types tissues, yet its role fibroblasts has not been explored. Utilizing gain- loss-of-function studies, we found MKP1 promoted restored their sensitivity to apoptosis — effects determined be mainly dependent upon dephosphorylation p38α (p38α). Fibroblast-specific deletion peak bleomycin-induced largely abrogated subsequent resolution. Such was treating these transgenic mice with inhibitor VX-702. We conclude a critical antifibrotic brake whose inhibition necessary for injury.

Language: Английский

Citations

12
Regulation of myofibroblast dedifferentiation in pulmonary fibrosis DOI Creative Commons

Xuetao Ju,

Kai Wang, Congjian Wang

et al.

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 18, 2024

Abstract Idiopathic pulmonary fibrosis is a lethal, progressive, and irreversible condition that has become significant focus of medical research due to its increasing incidence. This rising trend presents substantial challenges for patients, healthcare providers, researchers. Despite the escalating burden fibrosis, available therapeutic options remain limited. Currently, United States Food Drug Administration approved two drugs treatment fibrosis—nintedanib pirfenidone. However, their effectiveness limited, they cannot reverse process. Additionally, these are associated with side effects. Myofibroblasts play central role in pathophysiology significantly contributing progression. Consequently, strategies aimed at inhibiting myofibroblast differentiation or promoting dedifferentiation hold promise as effective treatments. review examines regulation dedifferentiation, exploring various signaling pathways, regulatory targets, potential pharmaceutical interventions could provide new directions development.

Language: Английский

Citations

10