Consumption of Endogenous Caspase‐3 Activates Molecular Theranostic Nanoplatform against Inflammation‐Induced Profibrotic Positive Feedback in Pulmonary Fibrosis DOI Creative Commons
Qiuling Li, Xin Chang, Yuxuan Han

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

The limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents promising shortcut reverse Herein, specific molecular nanotheranostic (Casp-GNMT), which is triggered by endogenous cysteinyl aspartate proteinase-3 (caspase-3), boosts antifibrotic efficacy through bioimaging synergistic chemotherapy at level, facilitating ionizable lipid reactive oxygen species sensitive for precise manageable therapy. activation imaging probe (pCY-pairs) consumption caspase-3 initiates fluorescence resonance energy transfer-guided pattern, aiming restore mitochondrial dysfunction-induced oxidative stress inflammatory responses in alveolar epithelial cells II (AECs II). This process sequentially resists the expression interleukin-1β vascular endothelial growth factor receptor combined nintedanib, further suppressing abnormal AECs persistent migration proliferation cells. Especially, homeostasis injured diminishes excessive accumulation transforming factor-β restrain myofibroblasts collagen deposition, thereby amplifying possibility reversing proposed provide prompt exact approach enhance authenticity treating efficiency harnessing indicator PF reversal.

Language: Английский

Pharmacological targeting of ECM homeostasis, fibroblast activation, and invasion for the treatment of pulmonary fibrosis DOI
Ioannis Tomos,

Paraskevi Kanellopoulou,

Dimitris Nastos

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with dismal prognosis. While the standard-of-care (SOC) drugs approved for IPF represent significant advancement in antifibrotic therapies, they primarily slow progression and have limited overall efficacy many side effects. Consequently, remains condition high unmet medical pharmacological needs.

Language: Английский

Citations

1
Pulmonary fibrosis: pathogenesis and therapeutic strategies DOI Creative Commons
Jianhai Wang, Kuan Li,

De Hao

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 23, 2024

Abstract Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate function excessive accumulation extracellular matrix, leading to tissue scarring impaired respiratory function. Although our understanding its pathogenesis has increased, effective treatments remain scarce, fibrotic progression major cause mortality. Recent research identified various etiological factors, including genetic predispositions, environmental exposures, lifestyle which contribute the onset PF. Nonetheless, precise mechanisms these factors interact drive are not yet fully elucidated. This review thoroughly examines diverse molecular mechanisms, key signaling pathways involved in PF, such as TGF‐β, WNT/β‐catenin, PI3K/Akt/mTOR. It also discusses current therapeutic strategies, antifibrotic agents like pirfenidone nintedanib, explores emerging targeting senescence. Emphasizing need for omni‐target approaches overcome limitations therapies, this integrates recent findings enhance PF development more prevention management ultimately improving patient outcomes.

Language: Английский

Citations

4
Distinct cAMP regulation in scleroderma lung and skin myofibroblasts governs their dedifferentiation via p38α inhibition DOI Creative Commons
J.D. Baas, John Varga, Carol Feghali‐Bostwick

et al.

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

Published: March 1, 2025

Fibrosis in systemic sclerosis/scleroderma (SSc) is characterized by the progressive accumulation and persistence multiple organs of pathologic fibroblasts whose contractile properties exuberant secretion collagens promote tissue stiffness scarring. Identifying a tractable mechanism for inactivating possibly clearing these ultimate effector cells fibrosis, conventionally termed myofibroblasts (MFs), represents an appealing therapeutic strategy patients with SSc. This can be accomplished their phenotypic dedifferentiation, process known to promoted generation intracellular second messenger cyclic AMP (cAMP). Notably, however, abilities SSc derived from different tissues generate cAMP - dedifferentiate response it have never been directly or compared. Here we compared two processes lung skin MFs While increasing induced comparable dedifferentiation MFs, well-recognized stimulus prostaglandin E 2 (PGE ) was diminished absent as lung, part due differences expression its target G protein-coupled receptors (GPCRs). Importantly, treatment phosphodiesterase 4 inhibitor rescued dedifferentiating effects PGE MFs. Finally, both cAMP-mediated direct pharmacologic inhibition MAPK p38α We conclude that activation pathway subsequent dedifferentiates skin, may thus represent alleviate multi-organ fibrosis

Language: Английский

Citations

0
Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis DOI
Tianming Zhao, Yunchao Su

Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1), P. 10001 - 10001

Published: Jan. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and fatal disease with an increasing incidence limited therapeutic options. It characterized by the formation deposition of excess extracellular matrix proteins resulting in gradual replacement normal lung architecture fibrous tissue. The cellular molecular mechanism IPF has not been fully understood. A hallmark fibroblast to myofibroblast transformation (FMT). During excessive repair upon exposure harmful stimuli, fibroblasts transform into myofibroblasts under stimulation cytokines, chemokines, vesicles from various cells. These mediators interact fibroblasts, initiating multiple signaling cascades, such as TGFβ1, MAPK, Wnt/β-catenin, NF-κB, AMPK, endoplasmic reticulum stress, autophagy, contributing FMT. Furthermore, single-cell transcriptomic analysis revealed significant heterogeneity among myofibroblasts, which arise cell types are adapted altered microenvironment during pathological repair. This review provides overview recent research on origins pathways driving their formation, focus interactions between epithelial cells, endothelial macrophages context fibrosis. Based these insights, targeting FMT could offer promising avenues for treatment IPF.

Language: Английский

Citations

0
Capparis spinosa inhibits proliferation and fibrosis of myofibroblasts in systemic sclerosis through modulation of MAPK signaling DOI
Xiaolan Qi,

F. Lou,

Feng Sun

et al.

Molecular & Cellular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

Citations

0
SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts DOI Creative Commons
Tongzhu Jin, Huiying Gao, Yuquan Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
The role of cyclic adenosine monophosphate (cAMP) in pathophysiology of fibrosis DOI Creative Commons

Sophie L Harding-Fox,

Selim Cellek

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104368 - 104368

Published: May 1, 2025

Fibrosis, the excessive production and disorganised deposition of extracellular matrix proteins, can occur in any organ system, disrupting functionality causing fatality. The number, efficacy safety antifibrotic drugs are incredibly limited. Therapeutics which elevate intracellular cyclic adenosine monophosphate (cAMP) offer a potential solution. In this review, we present signalling mechanisms involved fibrosis pathophysiology, how cAMP its effectors might interact with these pathways, current preclinical clinical efforts field. elevating agents have to be future drug candidates, but further studies required, particularly develop tissue specific therapeutics.

Language: Английский

Citations

0
Scorpion Venom Heat-Resistant Synthetic Peptide Alleviates Neuronal Necroptosis in Alzheimer’s Disease Model by Regulating Lnc Gm6410 Under PM2.5 Exposure DOI Open Access

Chuhao Qin,

Dongsheng Li, Jiahui Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4372 - 4372

Published: May 4, 2025

Recent epidemiological studies have indicated that exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less in the ambient air (PM2.5) is significantly associated elevated risk developing Alzheimer’s disease (AD) and its progression. Scorpion venom heat-resistant synthetic peptide (SVHRSP) exhibits anti-inflammatory neuroprotective properties. However, exact ways which SVHRSP mitigates progression AD induced by PM2.5 are still unknown. Long non-coding RNA (lncRNA) plays a crucial role various biological processes. Necroptosis, form programmed cell death, has garnered considerable attention recent years. This study aims investigate whether Lnc Gm16410 neuronal necroptosis involved PM2.5-exacerbated mechanisms alleviating this process. Through establishment model mice vitro model, it was found could promote down-regulation Gm16410, thereby promoting AD. Behavioral tests showed alleviated cognitive impairment PM2.5-induced mice. WB, qRT-PCR, other molecular assays indicate regulates under via p38 MAPK pathway. potential regulator regulating alleviate exposure-induced necroptosis. These findings offer new insights into mechanism through accelerates AD, examined from perspective LncRNA. Furthermore, we targets for treatment prevention following investigating action

Language: Английский

Citations

0
Insights into interstitial lung disease pathogenesis DOI Open Access
Eirini Vasarmidi, Julie C. Worrell, Irma Mahmutovic Persson

et al.

Breathe, Journal Year: 2025, Volume and Issue: 21(2), P. 240261 - 240261

Published: April 1, 2025

This review summarises some of the key features interstitial lung diseases (ILDs) from a translational science point view and brings insights into potential therapeutic options. Genetic predisposition environmental factors like smoking, pollution infections significantly impact onset, progression treatment response in ILDs, highlighting need for personalised management. Fibroblasts are central to ILD pathology, influencing tissue microenvironment, immune cell interactions extracellular matrix (ECM) production, making them critical targets. Monocyte-derived M2 macrophages drive fibrosis idiopathic pulmonary by secreting cytokines remodelling ECM. Understanding macrophage subtypes their dynamics offers new possibilities. Chronic type 2 immunity contributes fibrosis, emphasising enhance protective markers order even out balance shift pathological responses treatments. Serum biomarkers Krebs von den Lungen-6 (KL-6), surfactant protein (SFTP) D, metalloproteinase-7 (MMP-7), C-C motif chemokine ligand (CCL)-18 valuable diagnosing predicting progression, although more research is needed clinical application. Animal models, especially bleomycin-based offer but challenges hyperinflation highlight careful model selection bridge preclinical findings.

Language: Английский

Citations

0
The Hidden Link Between Chronic Kidney Disease and Lung Injury DOI
Elizabeth F. Redente

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2024, Volume and Issue: 71(6), P. 628 - 629

Published: Aug. 13, 2024

"The Hidden Link Between Chronic Kidney Disease and Lung Injury." American Journal of Respiratory Cell Molecular Biology, 0(ja), pp.

Language: Английский

Citations

0