DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis DOI Creative Commons
Juan Wang, Zhenkun Xia, Bei Qing

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 23, 2024

Abstract Background Pulmonary fibrosis (PF) is a progressive and difficult-to-heal lung disease that poses significant threat to human life health. This study aimed investigate the potential pathological mechanisms of PF identify new avenues for treatment PF. Methods Clinical samples were collected assess effect disulfide-bond A oxidoreductase-like protein (DsbA-L) on TGF-β1-induced MLE-12 cell model bleomycin (BLM)-induced mice established. Changes in physiological morphology observed tissues. The degree apoptosis mitochondrial function was analyzed. expression relative cytokines examined. CD68 + /CD206 ratio determined indicate M2 macrophage polarization. Results DsbA-L upregulated patients with PF-like models. In vitro, overexpression exacerbated deposition extracellular matrix (ECM), apoptosis, inflammation, damage, whereas silencing exerted opposite effects. inhibited activation AKT1, NLRP3, SMAD3 by TGF-β1. cells limited polarization RAW264.7 towards phenotype. AKT1 agonist or NLRP3 reversed role inhibiting TGF-β1/SMAD3 pathway vivo, knockout protected from damage caused BLM. Conclusion exhibited profibrotic epithelial mice, which increased levels activate These findings could shed light clues comprehension

Language: Английский

A narrative review on lung injury: mechanisms, biomarkers, and monitoring DOI Creative Commons
Wei Fan,

Biyu Gui,

Xiaolei Zhou

et al.

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: Oct. 31, 2024

Lung injury is closely associated with the heterogeneity, severity, mortality, and prognosis of various respiratory diseases. Effective monitoring lung crucial for optimal management improved outcomes patients This review describes acute chronic diseases characterized by significant current clinical tools assessing health. Furthermore, we summarized mechanisms cell death observed in these highlighted recently identified biomarkers plasma indicative to specific types scaffold structure lung. Last, propose an artificial intelligence-driven model assess disease predict mortality prognosis, aiming achieve precision personalized medicine.

Language: Английский

Citations

6
METTL14-mediated m 6 A modification of DDIT4 promotes its mRNA stability in aging-related idiopathic pulmonary fibrosis DOI Creative Commons
Dan Li, Qian Li,

Yufeng Du

et al.

Epigenetics, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 7, 2025

Although N6-methyladenosine (m6A) may be related to the pathogenesis of fibrotic process, mechanism m6A modification in aging-related idiopathic pulmonary fibrosis (IPF) remains unclear. Three-milliliter venous blood was collected from IPF patients and healthy controls. MeRIP-seq RNA-seq were utilized investigate differential modification. The expressions identified regulator target gene validated using MeRIP-qPCR real-time PCR. Moreover, we established an animal model a senescent A549 cells explore associated molecular mechanism. Our study provided panorama methylation IPF. Increased peaks (3756) decreased (4712) observed group. association analysis showed that 749 DEGs affected by Among regulators, expression METTL14 level our interested DDIT4 significantly, but mRNA higher This further verified bleomycin-induced fibrosis. At cellular level, it confirmed might participate senescence alveolar epithelial cells. downregulation inhibit decay reducing mRNA, leading high protein. alterations discovered as potential intervention for epigenetic These results pave way future investigations regarding modifications

Language: Английский

Citations

0
MBD2 promotes epithelial-to-mesenchymal transition (EMT) and ARDS-related pulmonary fibrosis by modulating FZD2 DOI
Yang Zhou, Guifang Yang, Jiqiang Liu

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167798 - 167798

Published: March 12, 2025

Language: Английский

Citations

0
DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis DOI Creative Commons
Juan Wang, Zhenkun Xia, Bei Qing

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 23, 2024

Abstract Background Pulmonary fibrosis (PF) is a progressive and difficult-to-heal lung disease that poses significant threat to human life health. This study aimed investigate the potential pathological mechanisms of PF identify new avenues for treatment PF. Methods Clinical samples were collected assess effect disulfide-bond A oxidoreductase-like protein (DsbA-L) on TGF-β1-induced MLE-12 cell model bleomycin (BLM)-induced mice established. Changes in physiological morphology observed tissues. The degree apoptosis mitochondrial function was analyzed. expression relative cytokines examined. CD68 + /CD206 ratio determined indicate M2 macrophage polarization. Results DsbA-L upregulated patients with PF-like models. In vitro, overexpression exacerbated deposition extracellular matrix (ECM), apoptosis, inflammation, damage, whereas silencing exerted opposite effects. inhibited activation AKT1, NLRP3, SMAD3 by TGF-β1. cells limited polarization RAW264.7 towards phenotype. AKT1 agonist or NLRP3 reversed role inhibiting TGF-β1/SMAD3 pathway vivo, knockout protected from damage caused BLM. Conclusion exhibited profibrotic epithelial mice, which increased levels activate These findings could shed light clues comprehension

Language: Английский

Citations

1