The graft response to transplantation: a gene expression profile analysis

Author:

Christopher Kenneth1,Mueller Thomas F.1,DeFina Rachel1,Liang Yurong1,Zhang Jianhua2,Gentleman Robert2,Perkins David L.1

Affiliation:

1. Laboratory of Molecular Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School

2. Biostatistics Unit, Department of Biostatistical Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Abstract

Little is known regarding the graft response to transplantation injury. This study investigates the posttransplantation response of genes that are constitutively expressed in the heart. Constitutive heart and lymph node tissue-restricted gene expression was first analyzed with DNA microarrays. To demonstrate changes following transplantation in genes constitutively expressed in the heart, we performed vascularized murine heart transplants in allogeneic (BALB/c to B6), syngeneic (B6 to B6), and alymphoid (BALB/c-RAG2−/− to B6-RAG1−/−) experimental groups. Temporal induction of genes posttransplant relative to constitutive expression was evaluated with DNA microarrays. Dendrograms and self-organizing maps were generated to determine the dissimilarity between the experimental groups and to identify subsets of differentially expressed genes within the groups, respectively. Expression patterns of selected genes were confirmed by real-time PCR. Biological processes were assigned to genes induced posttransplant using the AnnBuilder package via the Gene Ontology Database. Post-transplant, a shift was noted in genes classified as defense, communication, and metabolism. Our results identify novel components of the graft response to transplantation injury and rejection.

Publisher

American Physiological Society

Subject

Genetics,Physiology

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