Shegan Mahuang Decoction ameliorates pulmonary fibrosis progression by inhibiting CCL3-mediated NETosis.

Mitochondrial IRF3 drives pulmonary fibrosis by impairing mitophagy and triggering ferroptosis.

Targeting CX3CR1 inhibits silica-induced epithelial-mesenchymal transition and pulmonary fibrosis in mice via the NF-κB signaling pathway.

The TGF-β/Smad signaling pathway plays a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and is modulated by sphingolipid metabolism. Ceramide, a key intermediate in this pathway, is synthesized in various acyl-CoA chain lengths by ceramide synthases (CerS). However, the specific role of ceramide synthase 5 (CerS5) in pulmonary fibrosis remains unclear. Therefore, this study aimed to elucidate the role of CerS5 in fibrotic responses using human lung fibroblasts (HFL1), IPF-derived myofibroblasts (IPF-MyoFs), and a bleomycin-induced mouse model of pulmonary fibrosis. CerS5 knockdown attenuated TGF-β1-induced expression of α-smooth muscle actin (αSMA), collagen I, fibronectin, and phosphorylated Smad2/3 in both HFL1 cells and IPF-MyoFs. It also suppressed TGF-β1-induced nuclear translocation of Smad2/3. Notably, CerS5 knockdown reduced protein levels of Smad3 and Smad4 even in the absence of TGF-β1 stimulation. Smad4 knockdown replicated the effects of CerS5 knockdown by decreasing TGF-β1-induced expression of fibrotic markers, phosphorylated Smad2/3, and total Smad3 levels. In vivo, CerS5 knockout significantly reduced bleomycin-induced lung fibrosis and Smad3/4 expression. These findings suggest that CerS5 regulates fibrotic responses via modulation of Smad4 and the TGF-β1/Smad signaling pathway. Targeting CerS5 may therefore represent a promising therapeutic strategy for the treatment of IPF.

Targeting CXCR6 suppresses granuloma formation and pulmonary fibrosis through inhibiting Th17 responses in sarcoidosis.

SIRT6 activation attenuates inflammatory-fibrogenic events, improves lung function and survival in experimental pulmonary fibrosis.

Pericytes are specialized mural cells that ensheathe microvessels and play critical roles in maintaining vascular homeostasis, regulating angiogenesis, and coordinating tissue repair. Studies in the systemic circulation have established that pericytes contribute to the pathogenesis of major vascular diseases, including stroke, myocardial infarction, and retinopathy, increasing interest in understanding their roles in both health and disease. In contrast, our understanding of pericyte biology in the lung remains relatively limited. Over the past 15 years, a growing body of evidence emphasizes that lung pericytes actively participate in vascular remodeling and inflammatory responses, pointing to an important role for these cells in the pathogenesis of multiple pulmonary diseases. This comprehensive review synthesizes current knowledge on the molecular mechanisms governing lung pericyte function, with particular emphasis on key signaling pathways including PDGF-BB/PDGFRβ, TGFβ/ALK1/ALK5, VEGF/VEGFR, Angiopoietin/Tie2, Notch, Wnt, and sphingosine-1-phosphate (S1P). We examine how these pathways orchestrate pericyte recruitment, proliferation, differentiation, and phenotypic transitions through complex downstream signaling cascades involving kinases, transcription factors, and mechanotransduction mechanisms. The review further explores the multifaceted roles of pericytes in major pulmonary diseases, including acute lung injury and acute respiratory distress syndrome (ALI/ARDS), pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer, and lung infections.

Role of ferroptosis and autophagy in pulmonary diseases.

Study on mannose-modified panax notoginseng polysaccharide self-assembled micelles to reduce idiopathic pulmonary fibrosis in mice.

Sulforaphane attenuates oxidative stress and vascular remodeling in indium lung disease rats via mediating the NF-κB and Nrf2 pathways.

KLF4/FOXF1 axis alleviates silicosis fibrosis by modulating fibroblast behavior and extracellular matrix remodeling.

An innovative label-free approach for investigating epithelial-mesenchymal transition: pharmacological characterization of TGF-β1 effects in A549 cells.

Puerarin inhibits SiO2-induced pulmonary epithelial-mesenchymal transition via suppressing NF-κB activation: Insights from network pharmacology and experiment validation.

Pyraclostrobin triggers pulmonary inflammation, oxidative stress, and fibrosis in mouse via Wnt/β-catenin signaling.

Structural characterization and inhibitory activity against silicosis of a bioactive polysaccharide from Farfarae Flos.

Amphiregulin as a central dynamic network biomarker in inhaled polyhexamethylene guanidine triggered pulmonary fibrosis.

Objective: To investigate the predictive value of baseline serum KL-6 levels for acute exacerbation (AE) in patients with fibrotic interstitial lung disease (F-ILD). Methods: A single-center retrospective cohort study was conducted, enrolling 265 patients with fibrotic ILD diagnosed by multidisciplinary team (MDT) at Sichuan Provincial People's Hospital from July 2022 to November 2024, including 118 patients with idiopathic pulmonary fibrosis (IPF) and 147 patients with fibrotic connective tissue disease-associated ILD (CTD-ILD). Baseline data were collected, and the primary endpoint was the occurrence of AE during follow-up. Cox regression analysis was used to identify independent risk factors for AE, and ROC curve analysis was performed to evaluate predictive performance. Results: After a median follow-up of 20 months, 77 patients (29.1%) developed AE. Multivariate Cox regression showed that KL-6≥1 363.5 U/ml (HR=3.928, P<0.001) was an independent risk factor for AE. Baseline KL-6 predicted AE in F-ILD with an AUC of 0.795, and the optimal cutoff value was 1 363.5 U/ml. The combined model (KL-6+CA15-3+CYFRA21-1+DLCO%) achieved an AUC of 0.853. Subgroup analysis revealed that KL-6 had the highest predictive value in IPF patients (AUC=0.820), followed by CTD-ILD patients (AUC=0.774). Conclusion: Baseline serum KL-6 is an independent predictor of AE in patients with F-ILD, demonstrating good risk stratification capability, particularly with optimal performance in IPF.

SOX4 is a transcriptional activator for CTHRC1 in lung fibroblast activation.

FFA4 inhibits bleomycin-induced pulmonary fibrosis in mice by suppressing IL-33.

ZhuYang TongBi decoction ameliorates pulmonary fibrosis by degrading TGFBR via CAV1.