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Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model

ABSTRACT: Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model

PROVIDER: PRJNA564729 | ENA |

REPOSITORIES: ENA

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Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model

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

RNA-seq comparison of CD90- myCAFs and CD90+ myCAFs flow-sorted from murine PDAC tumors derived from the orthotopic transplantation of PDAC KPC T-LOH organoids

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

Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis.

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

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

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

Differential expression of murine syngeneic orthotopic glioblastoma tumour models

Project description:Bulk RNA sequencing analysis of murine syngeneic orthotopic GL261-luc2 and CT2A-luc glioblastoma tumour models

2023-11-01 | GSE215123 | GEO

Acute viral bronchiolitis

Project description:Acute viral bronchiolitis

| PRJNA450428 | ENA

Lung transplantation-induced cold ischemia–reperfusion injury in the murine lung

Project description:Lung transplantation-induced cold ischemia–reperfusion injury in the murine lung

| PRJNA924286 | ENA

Differential expression of murine syngeneic orthotopic glioblastoma tumour models

Project description:Differential expression of murine syngeneic orthotopic glioblastoma tumour models

| PRJNA888952 | ENA

A window into disease: Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome

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

Expression data from the orthotopic tumors of MES-SA

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

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