Serum Amyloid A3 Promoter-Luciferase Reporter Mice Are Useful for Early Drug-Induced Nephrotoxicity Detection.
Ayane KudoHaruka OsedoRahmawati AisyahNao YazawaTolulope Peter SaliuKenshu MiyataThanutchaporn KumrungseeNoriyuki YanakaPublished in: International journal of molecular sciences (2024)
Early detection of drug-induced kidney injury is essential for drug development. In this study, multiple low-dose aristolochic acid (AA) and cisplatin (Cis) injections increased renal mRNA levels of inflammation, fibrosis, and renal tubule injury markers. We applied a serum amyloid A3 (Saa3) promoter-driven luciferase reporter (Saa3 promoter-luc mice) to these two tubulointerstitial nephritis models and performed in vivo bioluminescence imaging to monitor early renal pathologies. The bioluminescent signals from renal tissues with AA or CIS injections were stronger than those from normal kidney tissues obtained from normal mice. To verify whether the visualized bioluminescence signal was specifically generated by the injured kidney, we performed in vivo bioluminescence analysis after opening the stomachs of Saa3 promoter-luc mice, and the Saa3-mediated bioluminescent signal was specifically detected in the injured kidney. This study showed that Saa3 promoter activity is a potent non-invasive indicator for the early detection of drug-induced nephrotoxicity.
Keyphrases
- drug induced
- liver injury
- dna methylation
- gene expression
- transcription factor
- high fat diet induced
- low dose
- adverse drug
- crispr cas
- oxidative stress
- high resolution
- insulin resistance
- type diabetes
- adipose tissue
- skeletal muscle
- ultrasound guided
- platelet rich plasma
- metabolic syndrome
- binding protein
- sensitive detection