Expression data from biopsies of CIT study patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72355 | GEO | 2015/09/10
SECONDARY ACCESSION(S): PRJNA295241
REPOSITORIES: GEO
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Project description:We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features A retrospective, single-centered cohort study was designed to compare the safety and efficacy of rATG versus BAS for induction in patients who received a renal transplantation from a deceased donor between January 2007 and December 2012. Recipients with CIT greater than 20 hours were included in this study. Patients were excluded if they had received a prior transplantation or dual organ transplantation. Patients were followed for 12 months post-transplantation or until patient death, graft lost or lost to follow up. Patients in the rATG group received 1.5 mg per kilogram of body weight given intravenously with the initial dose given intraoperatively. Subsequent doses were given daily through post-operative day 3, for a total dose of 4.5-6.0 mg per kilogram. Dosing was adjusted based on daily white blood cell and platelet counts. BAS (20 mg given intravenously) was administered intraoperatively and the subsequent dose on day 3 post-transplantation. All patients received maintenance immunosuppression with tacrolimus, prednisone and mycophenolate mofetil. In total. 230 patients were transplanted with a CIT > 20 hours; 174 and 56 patients received rATG and BAS induction, respectively. Gene expression profiling ws carried out on a subset (n=28) of these patients' post transplant biopsies. Of those 28 patients, 16 received rATG and 12 received BAS induction treatment.
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Project description:Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
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