The Spatially Resolved Kidney Transcriptome Signatures in Rat Models of Trauma-Induced Acute Kidney Injury.

Area of Science:

• Renal pathophysiology
• Trauma research
• Molecular biology

Background:

• Trauma is a major cause of mortality, with acute kidney injury (AKI) worsening patient outcomes.
• Hemorrhagic shock (HS) and rhabdomyolysis (RM) are key contributors to trauma-related AKI, but their combined renal effects are unclear.

Purpose of the Study:

• To elucidate the early renal responses to HS, RM, and their combination (RM-HS) in a clinically relevant rat model.
• To characterize the distinct and synergistic molecular and regional kidney signatures induced by these traumatic insults.

Main Methods:

• Utilized a rat model mimicking human trauma.
• Performed bulk and spatial transcriptomics on kidney tissue.
• Successfully adapted mouse spatial transcriptomics probes for rat tissue analysis.

Main Results:

• Rhabdomyolysis (RM) was identified as the primary driver of transcriptional changes in the kidney.
• The combination of RM and HS (RM-HS) induced a synergistic response associated with increased mortality.
• HS suppressed renal metabolic activity, whereas RM upregulated inflammatory and stress-response pathways, revealing distinct regional signatures.

Conclusions:

• Proposed a mechanistic framework for trauma-induced AKI involving tubular cell injury, mitochondrial dysfunction, altered lipid metabolism, PLIN2 expression, and ferroptosis.
• The findings advance understanding of trauma-associated renal injury.
• Identified potential novel biomarkers and therapeutic strategies for mitigating AKI in trauma patients.