cyclin-d1 has been researched along with Pulmonary-Fibrosis* in 8 studies
1 review(s) available for cyclin-d1 and Pulmonary-Fibrosis
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[Mechanisms of programmed cell death of effector T lymphocytes].
T cell adequate function is critical for defense against pathogens. Transient disruption of T cell homeostasis occurs when primarily naive cells undergo antigen-driven expansion and acquire effector functions. Effector T cells then either undergo programmed cell death (PCD, it occurs usually as massive apoptosis during the contraction phase of the immune response) or survive to become memory cells. Two main pathways of effector T cell PCD are discussed in the review: activation induced cell death (AICD), which is a form of extrinsic apoptosis, and neglect-induced death (NID), which is an intrinsic one. Initial studies using in vitro models supported a role of AICD, mostly initiated by TCR receptor triggering in immune contraction. However, it was not finally supported by either recent in vivo experiments or current review authors' clinical studies concerning primed T cell apoptosis in chronic inflammatory lower airway diseases. Actually, Bcl-2 family members seem to be critical for the culling of T cell responses. The antiapoptotic molecule Bcl-2 and its proapoptotic antagonist Bcl-2, both under upstream control of autocrine interleukin-2, are the most probable candidates for regulators of T cell contraction. Other possible mechanisms regulating the process of contraction such as death receptor ligation, the impact of cytokines, as well as the importance of transcription factor NF-κB, are discussed. Additionally, attention is turned to the potential role of T cell survival/apoptosis regulation in future therapies of some diseases, including tumors and lung fibrosis. Topics: Apoptosis; Apoptosis Regulatory Proteins; Cell Death; Cyclin D1; Humans; Interleukin-2; Lung Neoplasms; NF-kappa B; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Signal Transduction; T-Lymphocytes | 2013 |
7 other study(ies) available for cyclin-d1 and Pulmonary-Fibrosis
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Lanatoside C protects mice against bleomycin-induced pulmonary fibrosis through suppression of fibroblast proliferation and differentiation.
It has been established that lanatoside C, a FDA-approved cardiac glycoside, reduces proliferation of cancer cell lines. The proliferation of fibroblasts is critical to the pathogenesis of pulmonary fibrosis (PF), a progressive and fatal fibrotic lung disease lacking effective treatment. In this study we have investigated the impact of lanatoside C on a bleomycin (BLM)-induced mouse model of PF and through the evaluation of fibroblast proliferation and activation in vitro. We evaluated explanted lung tissue by histological staining, western blot analysis, qRT-PCR and survival analysis, demonstrating that lanatoside C was able to protect mice against BLM-induced pulmonary fibrosis. The proliferation of cultured pulmonary fibroblasts isolated from BLM-induced PF mice was suppressed by lanatoside C, as hypothesized, through the induction of cell apoptosis and cell cycle arrest at the G2/M phase. The Akt signalling pathway was involved in this process. Interestingly, the production of α-SMA, fibronectin, and collagen I and III in response to TGF-β1 in healthy mouse fibroblasts was suppressed following lanatoside C administration by inhibition of TGF-β1/Smad signalling. In addition, TGF-β1-induced migration in lung fibroblasts was also impeded after lanatoside C treatment. Together, our data revealed that lanatoside C alleviated BLM-induced pulmonary fibrosis in mice via attenuation of growth and differentiation of fibroblasts, suggesting that it has potential as a candidate therapy for PF patients. Topics: Animals; Apoptosis; Bleomycin; Cell Cycle Checkpoints; Cell Differentiation; Cell Proliferation; Cyclin D1; Cyclin E; Cytoprotection; Down-Regulation; Fibroblasts; Forkhead Box Protein O1; Lanatosides; Male; Mice; Mice, Inbred C57BL; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Pulmonary Fibrosis; Signal Transduction; Smad Proteins; Transforming Growth Factor beta | 2019 |
Bone marrow mesenchymal stromal cells attenuate silica-induced pulmonary fibrosis potentially by attenuating Wnt/β-catenin signaling in rats.
Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. Previous studies have shown that early intervention with bone marrow mesenchymal stem/stromal cells (BMSCs) has positive effect on anti-pulmonary fibrosis caused by silica dust. However, early intervention using BMSCs is not practical, and the therapeutic effects of BMSCs advanced intervention on pulmonary fibrosis have rarely been reported. In this study, we investigated the effects of advanced transplantation (on the 28th day after exposure to silica suspension) of BMSCs on an established rat model of pulmonary fibrosis.. Successful construction of a pulmonary fibrosis model was confirmed by H&E and Masson's trichrome staining on the 28th day after exposure to silica suspension. On the 56th day after exposure, pulmonary CT examination showed a relieving effect of BMSCs on silica-induced pulmonary fibrosis which was confirmed by H&E and Masson's trichrome staining. Treatment of BMSCs increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including Vimentin (Vim) and α-Smooth actin (α-SMA) after exposure to silica suspension. Furthermore, we found that Wnt/β-catenin signaling pathway is abnormally activated in silica-induced pulmonary fibrosis, and exogenous transplantation of BMSCs may attenuate their expression.. BMSC transplantation inhibits the EMT to alleviate silica-induced pulmonary fibrosis in rats and the anti-fibrotic effect potentially by attenuating Wnt/β-catenin signaling. ᅟ: ᅟ. Topics: Animals; beta Catenin; Bone Marrow Cells; Cell Proliferation; Cyclin D1; Epithelial-Mesenchymal Transition; Glycogen Synthase Kinase 3 beta; Hydroxyproline; Lung; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Phosphorylation; Pulmonary Fibrosis; Rats, Sprague-Dawley; Silicon Dioxide; Suspensions; Tomography, X-Ray Computed; Wnt Signaling Pathway | 2018 |
[Effects of fasudil on bleomycin-induced pulmonary fibrosis in mice and on the biological behaviors in NIH3T3 mouse fibroblast cell line].
To determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice and to determine the effects and mechanisms of fasudil on the biological behaviors in NIH3T3 mouse fibroblast cell line.. The BPF model was induced by a single dosage of 2.5 mg/kg bleomycin intratracheal injection in mice and fasudil intraperitoneal injection was given to the mice. The fibrosis degree was determined pathologically by using the Ashcroft scoring method and biochemically by hydroxyproline assay in lung tissue. NIH3T3 mouse fibroblast cell line was cultured in vitro and fasudil was given to the cell. The proliferation activity in NIH3T3 cells were detected by MTT assay and flat colony forming experiment. The migration activity in NIH3T3 cells were detected by scratch test and transwell chamber experiment. The expression of CyclinD1, MMP2 and TIMP1 mRNA in NIH3T3 cells was detected by RT-PCR. The expression of CyclinD1, MMP2 and TIMP1 protein and the level of MYPT1 phosphorylation in NIH3T3 cells was detected by Western blot.. Compare to the mice administrated by bleomycin, the Ashcroft score and hydroxyproline content were significantly decreased in the mice administered fasudil. Administration of fasudil can reduce the ability of proliferation and migration in a dose-dependent manner in NIH3T3 cells. The effect of fasudil was possibly related to increase the production of TIMP1 and decrease the production of CyclinD1 and MMP2.. Administration of fasudil can attenuate pulmonary fibrosis both in vivo and in vitro. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis. Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Bleomycin; Cyclin D1; Fibroblasts; Lung; Matrix Metalloproteinase 2; Mice; NIH 3T3 Cells; Pulmonary Fibrosis; Reverse Transcriptase Polymerase Chain Reaction; Tissue Inhibitor of Metalloproteinase-1 | 2014 |
Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) may be triggered by epithelial injury that results in aberrant production of growth factors, cytokines, and proteinases, leading to proliferation of myofibroblasts, excess deposition of collagen, and destruction of the lung architecture. The precise mechanisms and key signaling mediators responsible for this aberrant repair process remain unclear. We assessed the importance of matrix metalloproteinase-3 (MMP-3) in the pathogenesis of IPF through i) determination of MMP-3 expression in patients with IPF, ii) in vivo experiments examining the relevance of MMP-3 in experimental models of fibrosis, and iii) in vitro experiments to elucidate possible mechanisms of action. Gene expression analysis, quantitative RT-PCR, and Western blot analysis of explanted human lungs revealed enhanced expression of MMP-3 in IPF, compared with control. Transient adenoviral vector-mediated expression of recombinant MMP-3 in rat lung resulted in accumulation of myofibroblasts and pulmonary fibrosis. Conversely, MMP-3-null mice were protected against bleomycin-induced pulmonary fibrosis. In vitro treatment of cultured lung epithelial cells with purified MMP-3 resulted in activation of the β-catenin signaling pathway, via cleavage of E-cadherin, and induction of epithelial-mesenchymal transition. These processes were inhibited in bleomycin-treated MMP-3-null mice, as assessed by cytosolic translocation of β-catenin and cyclin D1 expression. These observations support a novel role for MMP-3 in the pathogenesis of IPF, through activation of β-catenin signaling and induction of epithelial-mesenchymal transition. Topics: Adenoviridae; Animals; beta Catenin; Bleomycin; Cadherins; Cyclin D1; Disease Models, Animal; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Enzymologic; Genetic Vectors; Humans; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Protein Transport; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Transforming Growth Factor beta | 2011 |
Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis.
1. Pravastatin is best known for its antilipidemic action. Recent studies have shown that statins have immunomodulatory and anti-inflammatory effects. The present study aimed to determine whether or not pravastatin can attenuate acute lung injury and fibrosis in a mouse model. 2. Bleomycin was given to C57BL6 mice through intratracheal instillation. Pravastatin was given through intraperitoneal injection. To study the effect of pravastatin on the early inflammatory phase and the late fibrotic phase, mice were killed on days 3, 7, 14 and 21. 3. Pravastatin attenuated the histopathological change of bleomycin-induced lung injury and fibrosis. The accumulation of neutrophils and increased production of tumor necrosis factor-α in bronchoalveolar lavage fluid were inhibited in the early inflammatory phase. Pravastatin effectively inhibited the increase of lung hydroxyproline content induced by bleomycin. Furthermore, pravastatin reduced the increased expression of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), RhoA and cyclin D1. The increased levels of TGF-β1 and CTGF mRNA expression were also significantly inhibited by pravastatin. 4. Pravastatin effectively attenuated bleomycin-induced lung injury and pulmonary fibrosis in mice. Our results provide evidence for the therapeutic potential of pravastatin in the treatment of acute lung injury and pulmonary fibrosis. Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bleomycin; Blotting, Western; Bronchoalveolar Lavage Fluid; Connective Tissue Growth Factor; Cyclin D1; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Hydroxyproline; Mice; Mice, Inbred C57BL; Pravastatin; Pulmonary Fibrosis; Respiratory Distress Syndrome; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins; rhoA GTP-Binding Protein; Transforming Growth Factor beta1 | 2010 |
Beta-catenin in the fibroproliferative response to acute lung injury.
Resolution of alveolar epithelial/capillary membrane damage after acute lung injury requires coordinated and effective tissue repair to reestablish a functional alveolar epithelial/capillary membrane barrier. We hypothesized that signaling pathways important in lung alveolar bud ontogeny are activated in the recovery and remodeling phases after profound oxidant stress lung injury in a murine model. To test this, we characterized the expression of noncanonical beta-catenin pathway proteins E-cadherin, integrin-linked kinase-1, and beta-catenin in mice undergoing normoxic recovery after exposure to butylated hydroxytoluene (BHT, ionol) and concomitant sublethal (75% O2) hyperoxia. Mice developed early acute lung injury with subsequent inflammation, collagen deposition, interstitial cellular proliferation, and lung architectural distortion. Reduced E-cadherin expression after 6 d of BHT and hyperoxia was accompanied by enhanced expression and nuclear localization of beta-catenin and increased integrin-linked kinase-1 expression during subsequent normoxic recovery. This resulted in increased expression of the cotranscriptional regulators TCF-1 and -3 and cyclin D1. Proliferation of murine lung epithelial-12 cells in vitro after 8 h of treatment with BHT quinone-methide and hyperoxia and 48 h of normoxic recovery was enhanced 2.7-fold compared with vehicle-treated control mice at the same time point. BHT/hyperoxia-exposed mice treated with the pan-caspase inhibitor z-ASP had increased acute lung injury and reduced survival despite the presence of TUNEL-positive cells, suggesting enhanced lung cell necrosis. Beta-catenin expression was reduced in z-ASP-co-treated lungs after BHT/hyperoxia. The noncanonical cadherin-beta-catenin axis is associated with fibroproliferative repair after BHT/hyperoxia exposure and may regulate epithelial proliferation and lung matrix remodeling and repair in response to lung injury. Topics: Animals; Apoptosis; Asparagine; beta Catenin; Butylated Hydroxytoluene; Cadherins; Caspase Inhibitors; Caspases; Cell Line, Transformed; Cell Proliferation; Collagen; Cyclin D1; Epithelial Cells; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Necrosis; Oxidative Stress; Oxygen; Protein Serine-Threonine Kinases; Pulmonary Fibrosis; Respiratory Distress Syndrome | 2006 |
RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis.
Idiopathic Pulmonary Fibrosis (IPF) is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression.. Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies.. Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p < 0.05). Serum deprivation inhibited cyclin D1 expression, which was restored following treatment with fibrogenic growth factors (TGF-beta1 and CTGF). RhoA inhibition, using a dominant negative mutant and a pharmacological inhibitor (C3 exotoxin), suppressed levels of cyclin D1 mRNA and protein in IPF fibroblasts, with significant abrogation of cell turnover (p < 0.05). Furthermore, Simvastatin dose-dependently inhibited fibroblast cyclin D1 gene and protein expression, inducing G1 cell cycle arrest. Similar trends were observed in control experiments using normal lung fibroblasts, though exhibited responses were lower in magnitude.. These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation. Topics: ADP Ribose Transferases; Botulinum Toxins; Cell Division; Cell Line; Connective Tissue Growth Factor; Cyclin D1; Fibroblasts; G1 Phase; Gene Expression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Lung; Pulmonary Fibrosis; rhoA GTP-Binding Protein; Signal Transduction; Simvastatin; Transforming Growth Factor beta; Transforming Growth Factor beta1; Up-Regulation | 2006 |