Abstract: SA-PO063
Sex Transcriptomic Signatures in Pig Kidneys After Ischemia-Reperfusion Injury and Recovery
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Meseguer, Anna, Vall d'Hebron Institut de Recerca, Barcelona, Spain
- Nemours, Stéphane, Vall d'Hebron Institut de Recerca, Barcelona, Spain
- Ribatallada, Didac, VHIR, Barcelon, Barcelona, Spain
- Aranda, Miguel, VHIR, Barcelon, Barcelona, Spain
- Castro, Luis, VHIR, Barcelon, Barcelona, Spain
Group or Team Name
- Renal Physiopathology Group. VHIR
Background
Renal ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Men are more prone to AKI and to CKD than women and it is accepted that androgens have a role in these processes. The mechanisms involved in injury/regeneration and the impact of gender remain to be fully elucidated. We propose that the identification of differentially expressed genes in male and female pig kidneys in basal, after injury and upon renal function might unravel genes and pathways useful to understand the different outcomes observed in men and women.
Methods
IRI was performed in single-kidney female and male pigs by clamping the renal artery for 30 minutes. Pre-ischemic, ischemic and post-ischemic kidney tissues (one week later) were collected for microarray assays. Pathway enrichment analysis and visualization of -omics data was done by GSEA, cytoescape and enrichment map. Systems biology-based mathematical models were also conducted to identify injury/recovery pathways and networks modulated in a sex-dependent manner.
Results
The numbers of genes differentially expressed in males versus females (adj P value 0.25) were 100 in pre-ischemic conditions, 858 at 5 min post-ischemia and 2 at one week pos-ischemia, indicating that although males were exhibiting differences in gene expression in basal situation and after injury, the general pattern of expression was similar to that of the females after one-week post-injury. Enriched pathways containing different gene sets down-regulated in males after one-week post-injury, but activated in basal situation and injury included, among others, immnune cell regulation, ion transpost transmembrane, steroid hormone response, type inteferon interleukins and intrinsic and extrinsic apoptosis. Contrarily, males after one-week have activated responses to growth factors such as the TGF-beta family members and extracellular matrix organization and collagen formation. Anaxomics systems biology patented technology has also pointed to STAT-1 and STAT-3 as crucial effectors of androgen mediated injury in kidney.
Conclusion
The targets identified in female and male pig samples together with the extensive bioinformatic analyses we have performed shall provide with novel mechanistic insights into the role of sex hormones in the kidney injury and regeneration processes.
Funding
- Government Support - Non-U.S.