The Role of p53-Mediated Cellular Senescence in Idiopathic Pulmonary Fibrosis.

An increasing body of evidence suggests that cellular senescence is a risk factor for the development of idiopathic pulmonary fibrosis (IPF). Cellular senescence is a permanent state by which cells cease to divide and adopt an irreversible cell cycle arrest, which is believed to contribute to aging and aging-related diseases. IPF is an age-related, chronic, progressive, and ultimately fatal interstitial lung disease of unknown etiology.

Inhibition of iron ion accumulation alleviates polystyrene nanoplastics-induced pulmonary fibroblast proliferation and activation.

Microplastics (MPs) and nanoplastics (NPs) are increasingly recognized as widespread environmental pollutants with significant ecological and human health implications, with particularly severe impacts on the respiratory system. This study aimed to explore the effects of polystyrene nanoplastics (PS-NPs, 80 nm) on pulmonary fibroblast proliferation and activation in NIH/3 T3 cells. Herein, we conducted a PS-NPs-induced fibroblast-to-myofibroblast transition (FMT) model and a pulmonary fibrosis mouse model.

Lysosomal Acidification: A New Perspective on the Pathogenesis and Treatment of Pulmonary Fibrosis.

Pulmonary fibrosis is a complex pathophysiological process characterized by local pulmonary inflammation and fibrosis, along with systemic inflammation and distal organ damage. The acidic environment of lysosomes, as intracellular degradation and recycling centers, is important for cellular homeostasis and function. This review summarizes the potential role of lysosomal acidification in pulmonary fibrosis pathogenesis and its implications for cross-organ effects.

Pulmonary fibrosis: from mechanisms to therapies.

Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by excessive deposition of extracellular matrix (ECM) and abnormal fibroblast proliferation, which is mainly caused by air pollution, smoking, aging, occupational exposure, environmental pollutants exposure, and microbial infections. Although antifibrotic agents such as pirfenidone and nintedanib, approved by the United States (US) Food and Drug Administration (FDA), can slow the decline in lung function and disease progression, their side effects and delivery inefficiency limit the overall prognosis of PF. Therefore, there is an urgent need to develop effective therapeutic targets and delivery approaches for PF in clinical settings.

Protein Ubiquitination Modification in Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a chronic, progressive fibrotic interstitial lung disease characterized by a high incidence and mortality rate, which encompasses features, such as diffuse alveolar inflammation, invasive fibroblast activation, and uncontrolled extracellular matrix (ECM) deposition. Beyond the local pathological processes, PF can be better understood in light of interorgan communication networks that are involved in its progression. Notably, pulmonary inflammation can affect cardiovascular, renal, hepatic, and neural functions, highlighting the importance of understanding these systemic interactions.

Bazibushen attenuates fibroblast senescence in silica-induced pulmonary fibrosis via FOXO1/PINK1/Parkin Axis.

Silicosis, an age-related disease, is still a heavy burden on global occupational health. Emerging evidence has revealed that targeting senescent cells may be a promising therapeutic strategy for silicosis. This study was designed to investigate the novel function of Bazibushen (BZBS), a known anti-aging drug, in improving silica-induced lung fibrosis.

Senescent alveolar type II epithelial cells-secreted GDF15 promotes silicosis progression via interfering intercellular communication.

Background: Silicosis is a chronic fibrotic pulmonary disease caused by consistent inhalation of respirable crystalline-free silica dust. The senescence of alveolar epithelial type II cells (ATII) is considered the initiation of pulmonary fibrosis. As a secreted protein, growth differentiation factor 15 (GDF15) was found intimately associated with the severity of lung diseases via senescence.

Senescent endothelial cell-derived Galectin 3 promotes silicosis through endothelial-fibroblast and endothelial-macrophage crosstalk.

Silicosis is an occupational and irreversible interstitial lung disease, which is caused by the inhalation of respirable crystalline silica. Recent studies suggested that the senescence of endothelial cells is implicated in the pathogenesis of lung diseases. However, the role of senescent endothelial cells in silicosis remains poorly understood.

Fatty Acid Oxidation-Glycolysis Metabolic Transition Affects ECM Homeostasis in Silica-Induced Pulmonary Fibrosis.

Silicosis is a fatal occupational pulmonary disease that is characterized by irreversible replacement of lung parenchyma by aberrant Exracellular matrix (ECM). Metabolic reprogramming is a crucial mechanism for fibrosis. However, how the metabolic rewiring shifts the ECM homeostasis toward overaccumulation remains unclear.

NUDT21 regulates lysyl oxidase-like 2(LOXL2) to influence ECM protein cross-linking in silica-induced pulmonary fibrosis.

Silicosis is a disease caused by prolonged exposure to silica dust. It is the most typical, rapidly progressive, and fatal form of pneumoconiosis. Currently, there is no specific medication available for the treatment of silicosis.

LGALS3 regulates endothelial-to-mesenchymal transition via PI3K/AKT signaling pathway in silica-induced pulmonary fibrosis.

Silicosis is a progressive and chronic occupational lung disease characterized by lung inflammation, silicotic nodule formation, and diffuse pulmonary fibrosis. Emerging evidence indicates that endothelial-mesenchymal transition (EndoMT) plays a crucial role in the development of silicosis. Herein, we conducted a SiO-induced EndoMT model and established a mouse model with pulmonary fibrosis by silica.

promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis.

Epithelial-mesenchymal transition (EMT) is a vital pathological feature of silica-induced pulmonary fibrosis. However, whether circRNA is involved in the process remains unclear. The present study aimed to investigate the role of in the silica-induced EMT and the underlying mechanisms.

The interplay of Cxcl10/Mmp14 monocytes and Ccl3 neutrophils proactively mediates silica-induced pulmonary fibrosis.

As a fatal occupational disease with limited therapeutic options, molecular mechanisms underpinning silicosis are still undefined. Herein, single-cell RNA sequencing of the lung tissue of silicosis mice identified two monocyte subsets, which were characterized by Cxcl10 and Mmp14 and enriched in fibrotic mouse lungs. Both Cxcl10 and Mmp14 monocyte subsets exhibited activation of inflammatory marker genes and positive regulation of cytokine production.

CircZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and its translation function.

Background: Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica.

IL33-mediated NPM1 promotes fibroblast-to-myofibroblast transition via ERK/AP-1 signaling in silica-induced pulmonary fibrosis.

Silicosis is a global occupational pulmonary disease due to the accumulation of silica dust in the lung. Lacking effective clinical drugs makes the treatment of this disease quite challenging in clinics largely because the pathogenic mechanisms remain obscure. Interleukin 33 (IL33), a pleiotropic cytokine, could promote wound healing and tissue repair via the receptor ST2.

UHRF1-mediated ferroptosis promotes pulmonary fibrosis via epigenetic repression of GPX4 and FSP1 genes.

Pulmonary fibrosis (PF), as an end-stage clinical phenotype of interstitial lung diseases (ILDs), is frequently initiated after alveolar injury, in which ferroptosis has been identified as a critical event aggravating the pathophysiological progression of this disease. Here in, a comprehensive analysis of two mouse models of pulmonary fibrosis developed in our lab demonstrated that lung damage-induced ferroptosis of alveolar epithelial Type2 cells (AEC2) significantly accumulates during the development of pulmonary fibrosis while ferroptosis suppressor genes GPX4 and FSP1 are dramatically inactivated. Mechanistically, upregulation of de novo methylation regulator Uhrf1 sensitively elevates CpG site methylation levels in promoters of both GPX4 and FSP1 genes and induces the epigenetic repression of both genes, subsequently leading to ferroptosis in chemically interfered AEC2 cells.

Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.

Background: Pulmonary fibrosis is a chronic progressive fibrotic interstitial lung disease characterized by excessive extracellular matrix (ECM) deposition caused by activated fibroblasts. Increasing evidence shows that matrix stiffness is essential in promoting fibroblast activation and profibrotic changes. Here, we investigated the expression and function of matrix stiffness-regulated ZNF416 in pulmonary fibrotic lung fibroblasts.

Promoting the overall energy profit through using the liquid hydrolysate during microwave hydrothermal pretreatment of wheat straw as co-substrate for anaerobic digestion.

Liquid hydrolysate (LH) derived from the microwave hydrothermal pretreatment (MHP) of wheat straw (WS) was anaerobically digested together with the solid residual to promote the overall energy profit. Different MHP temperatures (90, 120, 150, 180 °C) and retention times (10, 20, 40 min) were investigated. Increased MHP intensity generated plenty of VFAs (mainly acetate) and phenols in the LH, implying the double-side effect of LH on AD.

Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation.

Pulmonary fibrosis is a chronic and progressive interstitial lung disease associated with the decay of pulmonary function, which leads to a fatal outcome. As an essential epigenetic regulator of DNA methylation, the involvement of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) in fibroblast activation remains largely undefined in pulmonary fibrosis. In the present study, we found that TGF-β1-mediated upregulation of UHRF1 repressed beclin 1 via methylated induction of its promoter, which finally resulted in fibroblast activation and lung fibrosis both in vitro and in vivo.

Caveolin-1 and Its Functional Peptide CSP7 Affect Silica-Induced Pulmonary Fibrosis by Regulating Fibroblast Glutaminolysis.

Exposure to silica is a cause of pulmonary fibrosis disease termed silicosis, which leads to respiratory failure and ultimately death. However, what drives fibrosis is not fully elucidated and therapeutic options remain limited. Our previous RNA-sequencing analysis showed that the expression of caveolin-1 (CAV1) was downregulated in silica-inhaled mouse lung tissues.

ALKBH5 promotes lung fibroblast activation and silica-induced pulmonary fibrosis through miR-320a-3p and FOXM1.

Background: N-methyladenosine (mA) is the most common and abundant internal modification of RNA. Its critical functions in multiple physiological and pathological processes have been reported. However, the role of mA in silica-induced pulmonary fibrosis has not been fully elucidated.

PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis.

Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension.

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling.

Background: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.

CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner.

Pulmonary fibrosis develops when myofibroblasts and extracellular matrix excessively accumulate in the injured lung, but what drives fibrosis is not fully understood. Glycolysis has been linked to cell growth and proliferation, and several studies have shown enhanced glycolysis promotes pulmonary fibrosis. However, detailed studies describing this switch remain limited.