Pax Protein Depletion in Proximal Tubules Triggers Conserved Mechanisms of Resistance to Acute Ischemic Kidney Injury and Prevents Transition to Chronic Kidney Disease.
Jeffrey A BeamishAsha C TelangMadison C McElliottAnas Al-SuraimiMahboob ChowdhuryJenna T Ference-SaloEdgar A OttoRajasree MenonAbdul SoofiJoel M WeinbergSanjeevkumar R PatelGregory R DresslerPublished in: bioRxiv : the preprint server for biology (2023)
Identifying the molecular and genetic regulators unique to the nephron that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are two homologous nephron-specific transcription factors that are critical for kidney development and physiology. Here we report that proximal-tubule-selective depletion of Pax2 and Pax8 protects against both acute and chronic injury and induces an expression profile in the S3 proximal tubule with common features shared among diverse conditions that protect against ischemia. These findings highlight a new role for Pax proteins as potential therapeutic targets to treat AKI.
Keyphrases
- transcription factor
- chronic kidney disease
- liver failure
- stem cells
- drug induced
- respiratory failure
- end stage renal disease
- dna damage
- ischemia reperfusion injury
- gene expression
- genome wide
- cell therapy
- intensive care unit
- binding protein
- mouse model
- blood brain barrier
- amino acid
- protein protein
- mechanical ventilation
- subarachnoid hemorrhage
- bone marrow