Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model
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PROVIDER: PRJNA564729 | ENA |
REPOSITORIES: ENA
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Project description:Background: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. Methods: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). Results: A total of 1343 genes were differentially upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. Conclusions: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.
2019-09-11 | GSE137169 | GEO
Project description:BACKGROUND:Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS:Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). RESULTS:A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. CONCLUSIONS:Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.
| S-EPMC7209239 | biostudies-literature
Project description:Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB.
| S-EPMC3638989 | biostudies-literature
Project description:We investigated differences between CD90- myCAFs and CD90+ myCAFs flow-sorted from murine PDAC tumors derived from the orthotopic transplantation of PDAC KPC T-LOH organoids
2023-11-30 | GSE243828 | GEO
Project description:Background: Bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), is the major limitation to long-term survival after lung transplantation. The patho-anatomical correlate is progressive, fibrotic occlusion of the small airways, so-called obliterative bronchiolitis (OB) –lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. Methods: By combining laser-capture microdissection (LCM) and optimized sample preparation protocols for mass spectrometry (MS) we analyzed end-stage OB-lesions identified in explanted lungs from four end-stage BOS patients. Immunohistochemistry and immunofluorescence were used to follow selected proteins of interest on the tissue level. Results: We established protein signatures for in total 15 OB-lesions. A set of 12 proteins identified in all lesions included both distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66), thereby mirroring the histomorphological variation of the lesions. Conclusions: Even though being distinct and focal pathologic events, OB-lesions showed considerable variations in their protein content, most likely reflecting different disease pathways. Combining spatial information and advanced protein identification, this study provides molecular and morphological insights essential for a better understanding of the development of chronic rejection after lung transplantation.
2021-05-19 | PXD014171 | Pride
Project description:The spontaneous pulmonary metastasis model of human uterine sarcoma was established using GFP-expressed MES-SA cells. Several sublines with different metastatic potentials were generated by in vivo passaging. We used microarrays to identify the metastatic-related genes using the orthotopic tumors with different metastatic potentials. Orthotopic transplanted uterine sarcoma were observed after 3 weeks post-transplantation and the xenografted tumor reached about 2000 mm3 in additional 3 weeks. After 6 weeks post-transplantation, the animals were sacrificed under isoflurane anesthesia, and the tumors were resected. The GFP-positive regions were collected using Leica MZ10F fluorescent stereomicroscope. This study compared the gene expression profiling between the orthotopic tumors with high (H)- and low (L)-metastatic potentials.
2014-12-08 | E-GEOD-63937 | biostudies-arrayexpress
Project description:ADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear.In this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice.The proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression.These findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches.
| S-EPMC3928084 | biostudies-other
Project description:Acute viral bronchiolitis (NMS)
| PRJNA450429 | ENA
Project description:Acute viral bronchiolitis (PBMC)
| PRJNA450430 | ENA