Homologous recombination mediated DNA repair protects from Acute Kidney Injury
Josie A. Silvaroli1 and Navjot Pabla1
1Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive
Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Acute kidney injury (AKI) is a common clinical syndrome that is associated with adverse short and longterm sequelae. AKI usually occurs in the setting of other disorders, such as sepsis, rhabdomyolysis,
cardiovascular and oncological diseases, where the underlying disease and or associated therapy cause
abrupt loss of renal function. While the underlying pathophysiological mechanisms are incompletely
understood, renal tubular epithelial cell (RTEC) dysfunction and cell-death are the hallmarks and the
underlying cause of AKI. Recent studies have shown that DNA damage contributes to RTEC dysfunction
during AKI. However, due to the technical challenges in studying DNA repair in vivo, it remains unknown
if RTECs can repair their DNA during or after AKI. Here we have used a novel DNA repair reporter mouse
to demonstrate that functional homologous recombination (HR) mediated DNA repair occurs in RTECs
early during the development of Ischemia-reperfusion and Rhabdomyolysis associated AKI. Importantly,
RTEC-specific deletion of HR-linked DNA repair protein, BRCA1 exacerbates RTEC dysfunction and AKI.
Overall, our studies suggest that DNA repair pathways play a protective role during acute kidney injury
and is a promising target for therapeutic interventions.
Funding: The current study was supported by an American Heart Association Predoctoral Fellowship
(AHA-900765) to J.A.S and NIDDK 1R01DK132230 to N.P.