Browsing by Subject "Pulmonary fibrosis"
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- PublicationOpen AccessAlterations in the alveolar epithelium after injury leading to pulmonary fibrosis(Murcia : F. Hernández, 1996) Kasper, M.; Haroske, G.This review discusses current knowledge of the involvement of the alveolar epithelium in tissue remodelling during fibrogenesis. The purpose of the present paper is to give an overview, including the authors' own results, of knowledge of ultrastructural alterations, proliferation kinetics and phenotypic changes of pneumocytes in experimental and clinical pathology of pulmonary fibrosis. After lung injury, the alveolar epithelial cells show ultrastructural alterations, hypertrophy and hyperplasia, and a modulation of a series of structural and membrane proteins such as cytoskeletal changes, loss or de novo expression of epithelial adhesion molecules, and altered lectin binding. Furthermore, enhanced secretion of proteases, of cytokines and other soluble factors can be observed in the alveolar epithelium. These findings suggest the contribution of the epithelium in the remodelling process to be greater than expected. Estimations of the cell kinetics show that type 11 pneumocytes have the proliferative capacity to restore high proportions of damaged type 1 cells within few hours. In fibrosis this capacity also seems to be affected seriously, resulting in transitional phenotypes between type 11 and type 1 cells. Additionally, in the light of the detection of CD44 type of adhesion molecules at the foot processes of type 11 pneumocytes, some aspects of epithelial-fibroblast interaction are described.
- PublicationOpen AccessButylated hydroxytoluene induces type-V collagen and overexpression of remodeling genes/proteins in experimental lung fibrosis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Martins, Vanessa; Teodoro, Walcy Rosolia; Pereira Velosa, Ana Paula; Andrade, Priscila; Farhat, Cecília; Fabro, Alexandre Todorovic; Capelozzi, Vera LuizaAnomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V. Female mice C57BL/6 (n=6) were instilled intraperitoneally with 400mg/kg of BHT dissolved in 1 mL of corn oil and euthanized at day 14 or 21 after BHT administration. Morphometry, immunohistochemistry and transmission electron microscopy were performed to characterize microscopic and submicroscopic changes of AECs and endothelial cells through transforming growth factor beta (TGF-β) basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression. Immunofluorescence and immunogold electron microscopy were performed to characterize Col V. Quantitative polymerase chain reaction (qPCR) was used to confirm differential levels of RNA messenger. BHT lungs showed marked fibrotic areas and hyperplastic AECs. The alveolar damage caused destruction of elastic fibers and a critical increase of Col V in ECM of distal lung parenchyma. Fibrogenesis-promoting markers TGF-β, bFGF and VEGF were also overexpressed in situ, coinciding with up-regulation in remodeling enzymes, growth factors, cytokines, transduction and transcription genes. BHT alters distal lung parenchyma signaling involved in pulmonary fibrosis highlighted similarities to human IPF in a pathway involving Col V arising as a promissory model to identify effective therapeutic targets.
- PublicationOpen AccessDian sanguis draconis improves pulmonary fibrosis by activating autophagy to regulate the PA/PAI-1 balance(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Song Jiayi; Li Qian; Yang Chunyan; Liu Qing; Li Jianmei; Fu Yi; Biología Celular e HistologíaBackground. Pulmonary fibrosis (PF) is a severe lung disease that manifests as lung tissue destruction and collagen deposition and easily leads to respiratory failure. It is difficult to reverse these conditions using current treatment methods. This study focused on the exploration and development of novel drugs for the treatment of PF. Methods. This study simulated the pathological process of PF by using a bleomycin (BLM)-induced rat model and a TGF-β1-induced in vitro cell model. Dian sanguis draconis (DSD) was used for intervention, and the effects on the lung tissue structure, collagen fiber deposition, autophagy level and PA/PAI-1 balance were evaluated via pathological tissue staining, western blotting, and ELISA. Results. In untreated PF rats, severely disordered lung tissue, thickened alveolar septa, and excessive deposition of collagen fibers were observed. In addition, the level of autophagy was inhibited, and the balance of PA/PAI-1 in the lung tissue was disrupted. After treatment with DSD, these pathological injuries improved, as demonstrated by the restoration of lung tissue structure, reduction in collagen fiber deposition, recovery of autophagy levels, and remodeling of the PA/PAI-1 balance. In addition, mechanistically, DSD improves PF by increasing the level of autophagy-related proteins and regulating the PA/PAI-1 balance. Conclusion. This study confirmed the significant effect of DSD in alleviating PF. These findings provide new drug candidates for the treatment of PF
- PublicationOpen AccessLong noncoding RNAs in respiratory diseases(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Zhang, Jiaxiang; Zhu, Yong; Wang, RuilanRecently developed RNA microarrays and high-throughput sequencing techniques have demonstrated that long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes. Emerging evidence has confirmed the relevance of lncRNAs to diverse types of human disease, including cancer and cardiovascular disease. In this review, we discuss the important functions of lncRNAs in respiratory diseases. Because the reviewed studies have mainly focused on non-small cell lung cancer, future work will need to extend the studies into other respiratory diseases. From a clinical perspective, targeting lncRNAs as a novel therapeutic strategy in respiratory diseases will require further study to further clarify their biological functions.
- PublicationOpen AccessMicroRNA-141-3p mediates epithelial cell proliferation, apoptosis, and epithelial-mesenchymal transition and alleviates pulmonary fibrosis in mice via Spred2(2023) Zhu, Liang; Chen, Mo; Wang, Wenwen; Zhu, Jianing; Wu, HuaxiangObjective. This study probed the mechanism of microRNA (miR)-141-3p in the progression of pulmonary fibrosis (PF). Methods. Mice were intratracheally administered with bleomycin (BLM) to establish a PF mouse model. To investigate the effects of miR-141-3p/Spred2 on PF in mice, PF mice received tail vein injections with agomir-141-3p and/or adenovirus vectors overexpressing Spred2 one week after BLM treatment. Then, the pathological changes of lung tissues were analyzed with H&E and Masson’s trichrome staining, and hydroxyproline contents in lung tissues were measured. For cell experiments, after loss- and gain-of-function assays, the role of miR-141-3p/Spred2 in the apoptosis and viability of TGF-β1-stimulated MLE-12 cells was examined by flow cytometry and CCK-8 assay, respectively. miR-141-3p, Spred2, COl 1, and α-SMA expression was determined in cells and mice. Then, the binding of miR-141-3p to Spred2 was tested with a dualluciferase reporter assay. Results. There were abnormally upregulated Spred2 and downregulated miR-141-3p in lung tissues of PF mice. TGF-β1 decelerated viability and augmented apoptosis and COl 1 and α-SMA expression in MLE-12 cells. Spred2 knockdown diminished apoptosis and αSMA and COl 1 expression while enhancing proliferation in TGF-β1-treated MLE-12 cells. Mechanistically, Spred2 was a target gene of miR-1413p. miR-141-3p upregulation accelerated proliferation and repressed apoptosis and α-SMA and COl 1 expression in TGF-β1-treated MLE-12 cells, which was nullified by further overexpressing Spred2. miR-141-3p alleviated PF in mice by targeting Spred2. Conclusion. miR-141-3p negatively modulates Spred2 to promote proliferation and repress epithelialmesenchymal transition and apoptosis of epithelial cells, as well as ameliorating PF in mice
- PublicationOpen AccessMolecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Baltazar García, Elia A.; Vargas Guerrero, Belinda; Gasca Lozano, Luz E.; Gurrola Díaz, Carmen M.The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-β/Smad or Wnt/β-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.
- PublicationOpen AccessShensiqigui tablets alleviate bleomycin-induced pulmonary fibrosis by inhibiting the hedgehog/wnt-β-catenin pathway(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Ma Rui; Xie Yupeng; Dong Yuan; Yin Fan; Yang Jiong; Xu Fenghua; Biología Celular e HistologíaBackground. Pulmonary fibrosis (PF) is a refractory disease characterized by inflammation and fibrosis. Shensiqigui Tablets (SSQGT), a combination of Codonopsis pilosula, Astragalus, and Angelica, is a traditional Chinese medicine with anti-inflammatory and antioxidant properties. Therefore, SSQGT may be a potential therapeutic agent for managing PF. This study aimed to investigate the effects of SSQGT on PF and its potential mechanisms. Methods. This study established a mouse model of PF through a single intratracheal injection of bleomycin (BLM) and used a TGF-β1-induced HFL-1 cell model. The experiment included control, model (BLM/TGF-β1), and treatment groups (pirfenidone, compound Biejiaruangan tablet (BJRGT), low-dose SSQGT, medium-dose SSQGT, and high-dose SSQGT). Histopathological changes and collagen deposition in lung tissues were observed using Hematoxylin-Eosin (HE) and Masson staining. Inflammatory exudation in bronchoalveolar lavage fluid (BALF) was assessed using ELISA, including TNF-α, IL-1β, IL-6, and NO. Oxidative stress markers SOD, GSH, and Malondi-aldehyde (MDA) were measured using commercial kits. mRNA and protein expression levels in lung tissues and in vitro models, including α-SMA, vimentin, collagen I, caspase-3, TGF-β, and the Hedgehog/Wnt-β-catenin pathway, were evaluated using qRT-PCR and western blot analysis. Results. SSQGT significantly alleviated BLM-induced weight loss and lung injury in mice and reduced HYP levels and collagen deposition. Additionally, SSQGT improved oxidative stress markers (decreased MDA levels and increased SOD and GSH activity) and mitigated inflammatory responses (reduced TNF-α, IL-1β, IL-6, and NO levels) and (downregulated α-SMA, collagen I, caspase-3, and TGF-β). Further mechanistic analysis showed that SSQGT inhibited the Hedgehog/ Wnt-β-catenin pathway. Conclusion. SSQGT alleviates BLM- or TGF-β1-induced PF by reducing oxidative stress and inhibiting inflammation through the suppression of the Hedgehog/ Wnt-β-catenin pathway, suggesting its potential as a therapeutic agent for PF
- PublicationOpen AccessTelocytes and lung disease(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Song, Dongli; Cretoiu, Dragos; Cretoiu, Sanda M.; Wang, XiangdongTelocytes (TCs) represent a new distinct type of interstitial cells found in many organs, including lungs. TCs are mainly defined by a small cellular body from which arise very long (hundreds of micrometers) extensions named telopodes. During the last years, TCs were characterized in respect with their microRNA profiles, gene features and proteome signatures. Also, the ultrastructural 3D configuration was further elucidated by the aid of the FIB-SEM technology. TCs are able to communicate by homo- and heterocellular contacts with neighboring cells and are also able to transfer genetic information and signaling molecules to influence other cells by means of extracellular vesicle release. However, the exact function of lung TCs remains unclear. Here, we review the potential significance of TCs in the pathogenesis of pulmonary diseases. We will also discuss some future possibilities for targeting TCs as a potential therapeutic strategy.
- PublicationOpen AccessThe role of apoptosis in pulmonary fibrosis(Murcia : F. Hernández, 2004) Kuwano, K.; Hagimoto, N.; Nakanishi, Y.Pulmonary fibrosis is a common response to various injuries to the lung. The resolution of a fibroproliferative response after lung injury is key to survival. Although there are various initiating factors or causes, the terminal stages are characterized by proliferation and progressive accumulation of connective tissue replacing normal functional parenchyma. Conventional therapy consisting of glucocorticoids or immunosuppressive drugs is usually ineffective in preventing progression of fibrosis. Further understanding of the molecular mechanisms of endothelial and epithelial cell injury, inflammatory reaction, fibroblast proliferation, collagen deposition and tissue remodeling, should lead to the development of effective treatments against pulmonary fibrosis. Evidence that apoptosis plays an important role in the pathophysiology of pulmonary fibrosis has been accumulated. We overview the role of apoptosis in each of the pathogenic events which have emerged from animal models and human tissue studies.