Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids
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PROVIDER: PRJNA956835 | ENA |
REPOSITORIES: ENA
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Project description:Fetal lung tissue fragments were implanted into adult lungs and miRNA expression at day 7 were compared. microRNA-487-3p, 374-5p, and 20b-5p expression changed by more than 2-fold in corticosteroid administration groups.
2023-10-01 | GSE229936 | GEO
Project description:IntroductionThe lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells.MethodsFetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups.ResultsThe grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups.ConclusionsImplanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.
| S-EPMC10514393 | biostudies-literature
Project description:Bacterial lung infections are associated with strong infiltration of CD11b+ myeloid cells, which limit life-threatening disease, but also severely damage lung tissue. In a murine lung infection model with Streptococcus pneumoniae, we found intrinsic upregulation of CD11b on resident alveolar macrophages. Such CD11b expression was associated with transcriptomic and proteomic adaptations by alveolar macrophages, leading to the identification of specific molecules and pathways that depended on CD11b. In the absence of CD11b, the antimicrobial defense of alveolar macrophages was strongly reduced, and the production of neutrophil-recruiting chemokines was more pronounced. Moreover, CD11b expression limited the infection and prevented excessive alveolar damage. In conclusion, our study provides detailed molecular insights into the alveolar macrophage-specific immune response to Streptococcus pneumoniae lung infection and reveals profound CD11b-dependent alterations that are critical for effective antimicrobial immunity, neutrophil recruitment, and prevention of alveolar damage.
2023-10-08 | PXD035269 | Pride
Project description:Lung Adenocarcinoma Promotion by Air Pollutants RNA sequencing
| PRJEB59269 | ENA
Project description:The tips of secondary alveolar septae in day 6 neonatal mouse lung tissue were isolated using laser capture microscopy. RNA was isolated from pooled secondary alveolar tips and also from pooled neonatal day 6 whole lung tissue. The isolated RNAs were then amplified in parallel. Gene array profiling of the two RNA samples was performed. Gene expression in the secondary alveolar septal tips was compared to gene expression in the whole lung tissue. In this way, the genes that are expressed in the tip of secondary alveolar septae were identified as well as the genes that are enriched in the alveolar septal tips versus in whole lung tissue. Experiment Overall Design: We performed an experiment in which we used laser capture microscopy to collect 10,000 secondary alveolar tips from frozen sections of lung tissue obtained from many different day 6 neonatal mice obtained from different litters. In the same experiment, we also isolated RNA from pooled day 6 neonate whole lung tissue. The isolated RNAs were amplified in parallel and then hybridized to microarrays in parallel in order to profile and compare gene expression in the two samples. The entire experiment was performed twice with tissue from different litters. In addition, the amplified RNAs were hybridized to two different microarrays, at different times.
2008-06-12 | E-GEOD-4220 | biostudies-arrayexpress
Project description:Purpose: Our goal was to evaluate the pathways through which chorioamnionitis induces fetal lung maturation and how it interacts with a low-dose treatment with antenatal corticosteroids to further enhance fetal lung maturation. Methods: We treated pregnant rhesus macaque at 132 days (80% gestation) with intre-amniotic bacterla lipopolissacharide to model chorioamnionitis or a low-dose antenatal corticosteroids treatment with betamethasone-acetate (Beta-Ac 0.125mg/kg) or both treatments. Fetuses were delivered by c-section after 5 days and RNA-sequencing of whole lung tissue was performed. Another group of fetuses exposed to LPS was delivered 16h after treatment. Preterm controls were delivered at 132 days and term controls were delivered at 155 days and received no intervention. Results: Treatment with Beta-Ac in the setting of chorioamnionitis improves lung compliance and increases surfactant production relative to either treatment alone. RNA sequencing shows that these changes are mediated by suppression of proliferation and induction of mesenchymal cellular death. The combined exposure results in a mature-like transcriptomic profile with inhibition of extracellular matrix development by suppression of collagen genes and regulators of lung development. ACS and inflammation also suppressed signature genes associated with proliferative mesenchymal progenitors similar to the term lung. Conclusion: Treatment with ACS in the setting of inflammation may result in early respiratory advantage to preterm infants, but this advantage may come at a cost of abnormal extracellular matrix development which may be associated with increased risk of chronic lung disease.
2021-02-01 | GSE148645 | GEO
Project description:The tips of secondary alveolar septae in day 6 neonatal mouse lung tissue were isolated using laser capture microscopy. RNA was isolated from pooled secondary alveolar tips and also from pooled neonatal day 6 whole lung tissue. The isolated RNAs were then amplified in parallel. Gene array profiling of the two RNA samples was performed. Gene expression in the secondary alveolar septal tips was compared to gene expression in the whole lung tissue. In this way, the genes that are expressed in the tip of secondary alveolar septae were identified as well as the genes that are enriched in the alveolar septal tips versus in whole lung tissue. Keywords: Comparison of gene profiles in the tips of secondary alveolar septae versus in whole lung tissue of neonatal mice
2006-08-19 | GSE4220 | GEO
Project description:Lung Adenocarcinoma Promotion by Air Pollutants Whole Genome Sequencing
| PRJEB58221 | ENA
Project description:Our data show that Wnt and FGF signalling, and the downstream transcription factors NKX2.1 and TFAP2C, promote human alveolar or airway fate respectively. Moreover, we have functionally validated cell-cell interactions in human lung alveolar patterning. We show that Wnt signalling from differentiating fibroblasts promotes alveolar type 2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. Our organoid system recapitulates key aspects of human lung development allowing mechanistic experiments to determine the underpinning molecular regulation.
2022-02-28 | E-MTAB-11435 | biostudies-arrayexpress
Project description:The objective of this study was to examine transcriptional changes in alveolar macrophages early after reperfusion in a model of murine lung transplant.
2018-07-04 | GSE116583 | GEO