PLX277910

GSE153507: Comparison of the transcriptomic profiles of WT and complement C3-deficient mice with rhabdomyolysis-induced acute kidney injury

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Rhabdomyolysis is a severe condition caused by skeletal muscle damage, leading to acute kidney injury (AKI). We demonstrate that complement has a direct pathogenic role in rhabdomyolysis-induced AKI. Deposition of C3d in the tubules of patients and mice correlated with rhabdomyolysis-induced AKI. Moreover, C3-defiient mice with rhabdomyolysis had preserved renal function. Mechanistically, C3-deficiency attenuated strongly inflammatory and apoptotic components of the renal transcriptome, perturbed by rhabdomyolysis. Complement was activated intrarenal by the lectin pathway via collectin-11. It proceeded in a C4-bypass manner and was amplified by heme-activated alternative pathway. Therefore, complement and heme are promising therapeutic targets for rhabdomyolysis-induced AKI. SOURCE: Anne Grunenwald (annegrun@gmail.com) - INSERM UMRS1138 Cordeliers Research Center