Experimental Lung Research最新文献

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disorder that often leads to fatal outcomes, characterized by the aberrant proliferation of myofibroblasts and excessive deposition of extracellular matrix (ECM) components. Follistatin-like 1 (Fstl1), a secreted glycoprotein regulated by transforming growth factor β1 (TGF-β1), has been found to be markedly elevated in the fibrotic lungs of both patients with IPF and mice subjected to bleomycin-induced injury. Studies have shown that Fstl1 haploinsufficiency protects against bleomycin-induced lung injury, implicating Fstl1 as a potential therapeutic target. Here, we investigated the effect of Fstl1 knockdown using small interfering RNA (siRNA) on pulmonary fibrosis in vivo.

Methods: We designed four siRNA sequences targeting Fstl1 and evaluated their efficiency in mouse embryonic fibroblasts (MEFs). Of these, si-Fstl1-12 achieved maximal Fstl1 knockdown (∼80%) and significantly inhibited TGF-β1-induced upregulation of Fstl1 and ECM proteins in vitro. We used biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) nanomaterials as carriers for in vivo delivery. Bleomycin-treated mice were administered PLGA-si-Fstl1-12, and lung tissues were analyzed for Fstl1 expression, fibrosis severity, and collagen deposition.

Results: si-Fstl1-12 markedly suppressed TGF-β1-induced Fstl1 expression and ECM protein synthesis in MEFs in vitro. Treatment with PLGA-si-Fstl1-12 effectively reduced Fstl1 levels in lung tissue, attenuated interstitial fibrosis, and decreased collagen accumulation in bleomycin-challenged mice. Notably, even low doses of PLGA-si-Fstl1-12 achieved significant therapeutic effects, demonstrating efficient and safe siRNA delivery in vivo.

Conclusions: Targeted Fstl1 inhibition using siRNA significantly mitigated pulmonary fibrosis in a murine bleomycin model. The successful application of PLGA nanomaterials for siRNA delivery underscores their potential for safe and effective in vivo gene silencing. These findings highlight si-Fstl1 as a promising therapeutic candidate for IPF and support further investigation of RNA-based nanomedicine in fibrotic lung diseases.

Background: The carotid body is a small, highly vascularized organ located at the bifurcation of the common carotid artery and serves as the primary peripheral detector of arterial oxygen tension in mammals. Although its physiological role in ventilatory and autonomic reflexes has been extensively investigated, these functions are fundamentally dependent on its specialized anatomical organization. Objective: This review provides a comprehensive overview of the anatomical organization of the carotid body, highlighting how its gross morphology, microvascular architecture, cellular composition, and innervation support rapid oxygen sensing and chemosensory signal transmission.

Methods: Current evidence from anatomical, histological, ultrastructural, developmental, comparative, and experimental studies was critically reviewed to summarize the structural organization of the carotid body across mammalian species. Particular emphasis was placed on the relationships between vascular organization, cellular arrangement, and neural connectivity, as well as structural adaptations associated with chronic hypoxia and disease.

Results: The carotid body is characterized by an exceptionally dense capillary network, intimate neurovascular coupling, and glomerular clusters composed of excitable type-1 (glomus) cells surrounded by supportive type-2 (sustentacular) cells. These structural features facilitate efficient oxygen delivery, rapid detection of changes in arterial oxygen tension, and effective transmission of chemosensory information to the central nervous system. Comparative and developmental studies further demonstrate species-specific anatomical differences and substantial structural plasticity in response to chronic hypoxia, aging, and pathological conditions.

Conclusions: The specialized anatomy of the carotid body forms the structural basis of its remarkable sensitivity to changes in arterial oxygen tension. Integrating current knowledge of its vascular, cellular, and neural organization provides important insight into peripheral chemoreception and establishes an anatomical framework for understanding carotid body dysfunction in cardiopulmonary and metabolic diseases.

Background: Sepsis is a critical illness marked by widespread inflammation and failure of multiple organs. Pyroptosis and NLRP3 inflammasome activation play critical roles in sepsis pathogenesis. However, the involvement of interleukin-36 gamma (IL-36G) in this process remains unclear. This work probe to clarify the role and mechanism of IL-36G in sepsis-induced inflammation and lung injury.

Methods: RAW264.7 macrophages were exposed to lipopolysaccharide (LPS) to construct an in vitro model of sepsis. Cell viability, pyroptosis, and inflammatory cytokine expression were assessed by CCK-8 assay, flow cytometry, qPCR, and Western blot. The NF-κB pathway and NLRP3 inflammasome activation were evaluated following IL-36G overexpression or knockdown, with or without the NF-κB inhibitor BAY 11-7085. In vivo, a cecal ligation and puncture (CLP)-induced sepsis model was used in IL-36G knockout mice to assess lung injury and inflammatory responses.

Results: LPS stimulation induced pyroptosis and upregulated IL-36G expression in RAW264.7 cells, accompanied by increased levels of IL-6, IL-1β, TNF-α, and IL-18. IL-36G knockdown attenuated LPS-induced pyroptosis, inflammatory cytokine production, and expression of pyroptosis-related proteins. IL-36G overexpression activated the NF-κB pathway and enhanced NLRP3 inflammasome activation, while BAY 11-7085 inhibited these effects. In CLP-induced septic mice, IL-36G expression was upregulated, and its knockout improved survival, reduced the lung wet/dry (W/D) weight ratio, alleviated lung tissue damage, reduced inflammatory cytokine levels, and suppressed NF-κB-mediated NLRP3 inflammasome activation.

Conclusion: IL-36G promoted pyroptosis and NLRP3 inflammasome activation via NF-κB signaling pathway, contributing to sepsis-induced lung injury. Knockdown of IL-36G mitigated inflammation and tissue damage, indicating the therapeutic potential of IL-36G in sepsis.

Background: Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that results in progressive airway obstruction. Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of ABHD2 in the mechanisms of development of COPD-related sarcopenia. Methods: The involvement of ABHD2 was examined using in vivo CS-exposure model using ABHD2-KO mice. In CSE-induced COPD mouse models, ROS production and inflammation were measured using fluorescent probes and Western blot analysis. Results: Increased ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 and inhibiting Myod. ABHD2-KO mice with prolonged CS exposure showed enhanced muscle atrophy. Conclusion: These results indicated that ABHD2 played a key protective role in COPD-related skeletal muscle atrophy through a three-dimensional interactive network coordinating angiogenesis, oxidative stress defense, and inflammatory microenvironment regulation.

Aim: The diagnosis of neonatal respiratory distress syndrome NRDS relies on progressive breathing difficulties after birth, abnormal blood oxygen levels, and typical chest X-ray images. However, this diagnostic method has insufficient specificity and is difficult to make a differential diagnosis. Pulmonary surfactant replacement and respiratory support are the main treatment methods for NRDS, but targeted therapy is still lacking. Serum miRNA detection has high sensitivity and specificity. This study explored the miR-574-5p/RAB10 axis, providing potential molecular targets for the early diagnosis and treatment development of NRDS.

Materials and methods: This study included 110 non-NRDS and 110 NRDS newborns. The NRDS-related alveolar epithelial injury model was established by stimulating HPAEpiCs with LPS to verify the regulatory effect of the miR-574-5p/RAB10 signaling axis on the secretion of inflammatory factors. The level of miR-574-5p and RAB10 in serum and HPAEpiCs was detected by RT-qPCR. The secretion of inflammatory factors was tested by ELISA. The dual luciferase reporter gene assay was employed to investigate the targeting relationship between miR-574-5p and RAB10. The correlation between clinical factors and miR-574-5p expression was analyzed in NRDS by the chi-square test.

Results: The miR-574-5p expression was reduced in NRDS newborns and HPAEpiCs stimulated by LPS, while the RAB10 expression increased. The ELISA indicated that the secretion of inflammatory factors was increased in HPAEpiCs cells stimulated by LPS. The secretion levels of inflammatory factors were decreased after transfection with miR-574-5p mimic, while transfection with the miR-574-5p inhibitor, the secretion levels were increased. Overexpression of RAB10 overturned the anti-inflammatory role of miR-574-5p mimic.

Conclusions: This study demonstrated that the miR-574-5p/RAB10 signaling axis plays a crucial role in regulating the inflammation in NRDS. This not only provides potential molecular markers for the early diagnosis of NRDS but also identifies miR-574-5p as a potential therapeutic target for NRDS.

Aim of the study: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, and early screening is critical for improving patient outcomes. This review aims to provide a comprehensive theoretical foundation and practical guidance for developing more accurate and efficient COPD screening tools by summarizing the research progress in constructing COPD screening models based on respiratory oscillometry (RO).

Materials and methods: We conducted a narrative literature review of PubMed, Scopus, and Embase through May 2026 to identify studies on respiratory oscillometry-based COPD screening models, with particular attention to comparisons between traditional regression/discriminant approaches and machine-learning algorithms. Respiratory oscillometry (RO), a noninvasive and convenient method for assessing lung function, was used as the technical basis. The review systematically traces the evolution of COPD screening models from traditional statistical regression models to advanced machine learning approaches, analyzing technical characteristics, performance metrics, clinical applicability, and challenges associated with different modeling techniques.

Results: Key findings indicate machine learning algorithms outperform traditional logistic regression in COPD screening model accuracy, with RO technology demonstrating unique advantages in noninvasive lung function assessment through cross-comparison of modeling techniques.

Conclusions: This review confirms RO-based machine learning models as the optimal approach for COPD screening, providing critical guidance for developing next-generation tools to enhance early detection accuracy and clinical applicability.

Background: Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death worldwide and is primarily caused by cigarette smoke (CS) exposure. A reduction in the number of ciliated cells significantly contributes to the development and progression of COPD. Nicastrin (NCSTN), a core subunit of γ-secretase, plays an important role in the pathogenesis of various tumors. However, to date, no studies have demonstrated its role in COPD. The aim of this study was to investigate the effect and underlying mechanism of NCSTN on the differentiation of airway epithelial basal cells into ciliated cells under cigarette smoke extract (CSE) exposure. Methods: Mouse tracheal epithelial basal cells were differentiated at the air-liquid interface (ALI) in vitro and exposed to CSE for 7 days. Lentiviral overexpression and knockdown of NCSTN in basal cells were performed. The effects on cell differentiation, NCSTN expression and the Notch signaling pathway in response to CSE were assessed using reverse transcription‑quantitative PCR (RT-qPCR) and western blotting (WB). Results: We found that CSE exposure in vitro inhibited ciliated cell differentiation, while simultaneously increasing the expression of NCSTN, Notch3, and Hes1. Overexpression of NCSTN suppressed ciliated cell differentiation and induced Notch3 activation. Conversely, knockdown of NCSTN attenuated the CSE-mediated reduction in ciliated cell differentiation and inhibited Notch3 activation. Our findings indicate that CSE exposure inhibits basal cell differentiation into ciliated cells by upregulating the NCSTN-Notch3-Hes1 pathway. Conclusions: Inhibition of the NCSTN-Notch3-Hes1 pathway promoted ciliated cell differentiation and ameliorated the CSE-induced reduction in ciliated cells.

Cuproptosis, a recently identified form of regulated cell death, relies on accumulated copper (Cu) ions and a disrupted mitochondrial respiratory chain. The role of cuproptosis in various diseases, especially respiratory diseases of pulmonary fibrosis, chronic obstructive pulmonary disease, and lung cancer, has been increasingly recognized. This article reviews the dysregulation of Cu homeostasis, cuproptosis's molecular mechanisms, and recent research developments in respiratory diseases, while also exploring potential therapeutic targets and clinical applications.

Objective: Asthma development is significantly influenced by the abnormal proliferation and migration of human airway smooth muscle cells (HASMCs). The aim of this study was to investigate the role and molecular mechanisms of the m6A methyltransferase METTL3 in platelet-derived growth factor BB (PDGF-BB)-treated HASMCs. Methods: An in vitro model of HASMCs stimulation was constructed by PDGF-BB. Proliferation, migration, and levels of inflammatory factors of HASMCs were detected by CCK-8, Transwell assay, and ELISA, respectively. m6A modification sites in GAS5 were predicted using WHISTLE. m6A methylation level in GAS5 was detected by MeRIP-qPCR. The RNA stability of GAS5 was assessed by RNA decay assay. Targeted binding sites between miR-29c-3p and GAS5 or VAMP2 were predicted using starBase, and their targeting relationship was verified by dual-luciferase reporter assay. Results: METTL3 levels were decreased in PDGF-BB-induced HASMCs. Enhancing METTL3 expression in HASMCs inhibited PDGF-BB-induced proliferation, migration, and inflammation. METTL3-mediated m6A methylation decreased GAS5 stability, thereby inhibiting GAS5 expression. GAS5 targeted miR-29c-3p and regulated VAMP2 expression. In PDGF-BB-treated HASMCs, enhancing VAMP2 mitigated the effect of METTL3 upregulation. Conclusion: METTL3 inhibits HASMC proliferation, migration, and inflammation in asthma by regulating the GAS5/miR-29c-3p/VAMP2 axis.