|
| Status |
Public on Jan 28, 2015 |
| Title |
The Role of Macrophages in the Development of Human Renal Allograft Fibrosis in the First Year after Transplantation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The aim of this study was to investigate the role of infiltrating macrophages in renal allograft fibrosis. Forty-six protocol renal allograft biopsies obtained one-year after transplantation were stained with Sirius Red to quantify fibrosis and double stained with CD68 and CD206 to identify the proportion of alternately activated (M2) macrophages. 23 protocol biopsies obtained 12 months post transplant were analyzed for gene expression by microarray, which was correlated with macrophage infiltration and the severity of fibrosis. Phenotypic analysis showed 92% of infiltrating macrophages exhibited an M2 phenotype with CD68+CD206+ dual staining. Gene microarrays demonstrated a distinct alloimmune response despite the lack of rejection and inflammatory infiltrate with upregulation of interferon-γ-response genes. This suggests that following initiation of Th1 driven macrophage proliferation or infiltration, M2 macrophages contribute to tubular injury and progression of fibrosis.
|
| |
|
| Overall design |
23 protocol renal biopsies were obtained from patients at 12 month post transplant. The study population was divided into two groups according to the number of infiltrating macrophages (CD68 positive cells) (Group I: Recipients with a low number of infiltrating macrophages, CD68 positive cells < 400/mm2; Group II: Recipients with a high number of infiltrating macrophages, CD68 positive cells ≥ 400/mm2). Additional analyses were undertaken by dividing the group into those with fibrosis (ci score >1) and those without. To correlate gene expression with kidney fibrosis, or intensity of CD68 infiltrate, Spearman correlations analysis of the gene expression data with 12 month IFTA was performed and the correlation co-efficiency and its p value calculated. Gene Ontology enrichment and IPA pathway and network analysis (Ingenuity System Inc.) were performed on the associated genes. All p-values were two-sided, and p < 0.05 was considered significant.
|
| |
|
| Contributor(s) |
Toki D, Zhang W, Hor K, Murphy B, O'Connell P |
| Citation(s) |
25307039 |
| |
| Submission date |
Jan 27, 2015 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Philip John O'Connell |
| E-mail(s) |
philip.oconnell@health.nsw.gov.au
|
| Organization name |
Westmead Millennium Institute
|
| Department |
Centre for Transplant and Renal Research
|
| Street address |
176 Hawkesbury Rd
|
| City |
Westmead |
| State/province |
NSW |
| ZIP/Postal code |
2145 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (23)
|
|
| Relations |
| BioProject |
PRJNA273701 |
Less...
More...