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MicroRNAs Implicated in Dysregulation of Gene Expression Following Human Lung Transplantation

ABSTRACT: Lung transplantation remains the only viable treatment option for the majority of patients with advanced lung diseases. However, 5-year post-transplant survival rates remain low primarily secondary to chronic rejection. Novel insights from global gene expression profiles may provide molecular phenotypes and therapeutic targets to improve outcomes after lung transplantation. We compared whole-genome transcriptional expression profiled using the Affymetrix Human Exon Array in peripheral blood mononuclear cells (PBMCs) in lung transplant patients and normal individuals. 364 dysregulated genes in Caucasian lung transplant patients relative to normal individuals. Enriched Gene Ontology biological processes and pathways included defense response, immune response” and response to wounding”. We then compared the expression profiles of potential regulating miRNAs which suggested that dysregulation of a number of lung transplant-associated genes (e.g., ATR, FUT8, LRRC8B, NFKBIA) may be attributed to the differential expression of their regulating miRNAs. This exploratory analysis of the relationship between these miRNAs and their gene targets in the context of lung transplantation warrants further investigation and may serve as novel therapeutic targets in lung transplant complications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE49081 | GEO | 2014/07/20

SECONDARY ACCESSION(S): PRJNA212979

REPOSITORIES: GEO

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MicroRNAs Implicated in Dysregulation of Gene Expression Following Human Lung Transplantation

Project description:Lung transplantation remains the only viable treatment option for the majority of patients with advanced lung diseases. However, 5-year post-transplant survival rates remain low primarily secondary to chronic rejection. Novel insights from global gene expression profiles may provide molecular phenotypes and therapeutic targets to improve outcomes after lung transplantation. We compared whole-genome transcriptional expression profiled using the Affymetrix Human Exon Array in peripheral blood mononuclear cells (PBMCs) in lung transplant patients and normal individuals. 364 dysregulated genes in Caucasian lung transplant patients relative to normal individuals. Enriched Gene Ontology biological processes and pathways included defense response, immune response” and response to wounding”. We then compared the expression profiles of potential regulating miRNAs which suggested that dysregulation of a number of lung transplant-associated genes (e.g., ATR, FUT8, LRRC8B, NFKBIA) may be attributed to the differential expression of their regulating miRNAs. This exploratory analysis of the relationship between these miRNAs and their gene targets in the context of lung transplantation warrants further investigation and may serve as novel therapeutic targets in lung transplant complications. PBMC samples were collected from 18 patients (14 Caucasian Americans and 4 African Americans) who underwent single-lung transplant or bilateral single-lung transplant surgery during 2005-2008. Control samples were collected from healthy individuals (27 Caucasians and 8 African Americans). Whole-genome expression profiles were performed using the Affymetrix Human Exon 1.0ST Array. The expression levels of miRNAs were profiled using the Exiqon miRCURY™0. *This represents the Affymetrix Human Exon component of the study only.

2014-07-20 | E-GEOD-49081 | biostudies-arrayexpress

Lung transplantation for patients with severe COVID-19

Project description:Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-associated pneumonia in the native lung. Most importantly, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report results of the first successful lung transplantation procedures in patients with non-resolving COVID-19-associated respiratory failure in the United States. We performed sm-FISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. We used a machine learning approach to project single cell RNA-Seq data from patients with late stage COVID-19 onto a single cell atlas of pulmonary fibrosis, revealing similarities across cell lineages. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.

2020-10-28 | GSE158127 | GEO

Donor lung tissues: Control vs. Primary graft dysfunction (PGD)

Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (Â± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study Matched case-control observational study: 10 primary graft dysfunction cases vs 16 Good outcome cases. One replicate per array.

2008-09-15 | E-GEOD-9102 | biostudies-arrayexpress

Single cell RNA sequencing for normal and lymphangiogenesis-inhibiting vascular allografts

Project description:Transplant arteriosclerosis is a major limitation to long-term survival of patients with solid organ transplantation. Although lymphatic vessels have been recently reported to possess organ-specific features in allograft transplantation, the relationship between lymphangiogensis and transplant arteriosclerosis remains unknown.

2024-04-12 | GSE211731 | GEO

Expression of human lungs at cold ischemic time (CIT) and 1-2 hrs. after reperfusion (H)

Project description:Study on lung transplantation encompassing a comprehensive and detailed investigation of differences at transcription level between lungs before and after transplant.

2023-02-01 | GSE145989 | GEO

Post-transplant diabetes mellitus after kidney transplantation

Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)

2023-10-24 | PXD042188 | Pride

Heart Transplant Rejection Profiling in Peripheral Blood

Project description:PBMC samples from heart transplant patients were profiled. Sample classification was based on endomyocardial biopsy at the time of sample collection. Keywords = Transplant Keywords = Transplantation Keywords = Heart Transplant Keywords = Graft Rejection Keywords = Rejection Keywords = PBMC Keywords = Immune Response Keywords = Peripheral Blood

2010-06-10 | E-GEOD-2445 | biostudies-arrayexpress

Donor lung tissues: Control vs. Primary graft dysfunction (PGD)

Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study

2008-09-15 | GSE9102 | GEO

Heart Transplant Rejection Profiling in Peripheral Blood

2005-09-01 | GSE2445 | GEO

Validated Gene Expression Signatures of Idiopathic Pulmonary Fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets. 17 samples from 11 patients with IPF (6 patients provided a pair of samples from upper and lower lobes; 5 patients contributed singleton samples); 6 control specimens were obtained from routine lung volume reduction of healthy donor lungs at the time of lung transplantation.

2011-11-01 | E-GEOD-24206 | biostudies-arrayexpress

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