Proximal tubular transcriptional response to aristolochic acid

The proximal tubule is particularly susceptible to acute kidney injury caused by ischemic or toxic insults, due to its high oxygen demand, and role in excreting drugs such as DNA-damaging chemotherapeutics. AKI triggers PT cell de-differentiation, expression or pro-inflammatory and pro-fibrotic signaling molecules, and a dramatic shift in PT cell metabolism with severe suppression of fatty acid oxidation. The aim of this study was to investigate the transcriptional changes that occur in the S2 and S3 segments of the PT in response to the DNA damaging agent aristolochic acid I (AAI). Overall design: mRNA profiles were generated from combined S2/S3 kidney proximal tubules segments in control mice harvested 24 hours after injecting a single 3mg/kg dose of DMSO or AAI, using RNA-sequencing.