Identification of glycolysis-related gene signatures for prognosis and therapeutic targeting in idiopathic pulmonary fibrosis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Background Glycolysis plays a crucial role in fibrosis, but the specific genes involved glycolysis idiopathic pulmonary fibrosis (IPF) are not well understood. Methods Three IPF gene expression datasets were obtained from Gene Expression Omnibus (GEO), while glycolysis-related retrieved Molecular Signatures Database (MsigDB). Differentially expressed (DEGRGs) identified using “limma” R package. Diagnostic (GRGs) selected through least absolute shrinkage and selection operator (LASSO) regression support vector machine-recursive feature elimination (SVM-RFE). A prognostic signature was developed LASSO regression, time-dependent receiver operating characteristic (ROC) curves generated to evaluate predictive performance. Single-cell RNA sequencing (scRNA-seq) data analyzed examine GRG across various cell types. Immune infiltration analysis, Set Enrichment Analysis (GSEA), Variation (GSVA) performed elucidate potential molecular mechanisms. bleomycin (BLM)-induced mouse model used for experimental validation via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results 14 GRGs ( VCAN, MERTK, FBP2, TPBG, SDC1, AURKA, ARTN, PGP, PLOD2, PKLR, PFKM, DEPDC1, AGRN, CXCR4 ) as diagnostic markers IPF, with seven SDC1 forming demonstrating power (AUC: 0.831–0.793). scRNA-seq revealed cell-type-specific expression, particularly macrophages fibroblasts. analysis linked imbalanced immune responses. Experimental bleomycin-induced confirmed upregulation of (such CXCR4). Drug prediction inhibitors Tozasertib Plerixafor CXCR4) therapeutic agents. Conclusion This study identifies biomarkers highlights their modulating responses within fibrotic lung microenvironment. Notably, MERTK , associated pathways progression represent targets. Our findings provide insights into metabolic reprogramming suggest that targeting may offer novel pharmacological strategies antifibrotic therapy.

Language: Английский

---

Recent progress in exosomal non-coding RNAs research related to idiopathic pulmonary fibrosis

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterized by unknown etiology and limited therapeutic options. Recent studies implicate exosomal non-coding RNAs (ncRNAs) as crucial regulators in IPF. These ncRNAs, including long (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are involved cellular processes through various mechanisms of selective packaging, intercellular communication, signaling pathway integration. LncRNAs such LINC00470 PVT1 exhibit pro-fibrotic effects, while others like lnc-DC THRIL show inhibitory roles; some, UCA1 MALAT1, demonstrate bidirectional regulation. In miRNAs, agents (e.g., miR-486, miR-223) contrast with miRNAs miR-34a, miR-126), miR-21 miR-155 display dual functions. Similarly, circRNAs circ_0000479 circ_0026344 promote fibrosis, whereas circ_0000072 circ_0000410 act inhibitors, certain circ_002178 circ_0001246) exhibiting complex regulatory effects. Exosomal ncRNAs modulate key pathways, TGF-β Wnt/β-catenin, influencing IPF progression. Despite their potential, challenges remain exosome isolation, functional characterization clinical translation. Addressing these barriers innovative research strategies essential to leverage the management treatment This review comprehensively examines roles IPF, elucidates interactions, discusses future perspectives enhance understanding for this disease.

Language: Английский

---

Pathophysiologie der Fibrose – entzündlich vs. nichtentzündlich

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Fibrosis is characterized by an excessive accumulation of extracellular matrix components produced connective tissue cells. It a pathophysiological feature many chronic inflammatory diseases. Nearly every the body can be affected fibrosis. Its progression lead to dysfunction and organs potentially death. Early fibrotic mechanisms include activation immune responses leading cells misdirected wound healing responses, finally scarring Different pathways factors contribute pathophysiology fibrosis are summarized in this review.

Language: Английский

---

Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(9), P. 3118 - 3118

Published: April 30, 2025

Background: The global health burden of chronic respiratory diseases, such as obstructive pulmonary disease (COPD), asthma, idiopathic fibrosis (IPF), and acute distress syndrome (ARDS) affects billions people is associated with high levels healthcare expenditure. Conventional therapies (bronchodilators corticosteroids) provide symptomatic benefit but take no effect on progression, demonstrating the need to develop new therapies. Emerging treat underlying mechanisms these which relief disease. Methods: This review assesses evolution therapeutic interventions for lung diseases from a series established inhaled combination biologics, gene therapy, even AI-based stratification patients. In addressing issues, we action, evidence efficacy, clinical trial evidence, while discussing access issues affecting implementation ethical in relation their use. Results: highlights recent developments treatment approaches, aimed at cystic mutations, advanced drug delivery pathways more accurate targeting, stem cell-based designed replace damaged tissue. These have potential improve outcomes challenges, including lack access, adequate patient selection, long-term safety, be addressed. Conclusions: New offer tremendous potential, transition laboratory clinic still face numerous barriers regulation, personalized therapy approaches. indicates that future research should strategies reduce distribution, guidelines successfully implement

Language: Английский

---

miR-21 in cardiovascular disease: new insights and emerging therapeutic potential

Deleted Journal, Journal Year: 2025, Volume and Issue: 7(5)

Published: May 3, 2025

Language: Английский

---

Circulating MicroRNAs in Idiopathic Pulmonary Fibrosis: A Narrative Review

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(12), P. 13746 - 13766

Published: Dec. 4, 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic, deathly disease with no recognized effective cure as yet. Furthermore, its diagnosis and differentiation from other diffuse interstitial diseases remain challenge. Circulating miRNAs have been measured in IPF proven to be an adequate option biomarkers for this disease. These miRNAs, released into the circulation outside cell through exosomes proteins, play crucial role pathogenic pathways mechanisms involved development. This review focuses on serum/plasma reported that validated by real-time PCR published evidence regarding fibrotic process. First, we describe which travel (contained bound proteins), well mechanism perform their function within cell. Subsequently, summarize concerning serum/plasma, where find contradictory functions some (dual IPF) when comparing findings vitro vs. vivo. The most relevant finding, instance, levels of let-7d miR-21 IPF, correspond those found studies lung fibroblasts murine bleomycin model, reinforcing usefulness these future IPF.

Language: Английский

---