Mice with a < em > Pax2 < /em > missense variant display impaired glomerular repair

Am J Physiol Renal Physiol. 2024 Mar 14. doi: 10.1152/ajprenal.00259.2023. Online ahead of print.ABSTRACTPAX2 regulates kidney development and its expression persists in parietal epithelial cells (PECs), potentially serving as a podocyte reserve. We hypothesize that mice with a Pax2 pathogenic missense variant (Pax2A220G/+) have impaired PEC-mediated podocyte regeneration. Embryonic wild type mouse kidneys showed overlapping expression of PAX2/WT-1 until PEC and podocyte differentiation, reflecting a close lineage relationship. Embryonic and adult Pax2A220G/+ mice have reduced nephron number but demonstrated no glomerular disease under baseline conditions. Pax2A220G/+ compared to wild type mice were more susceptible to glomerular disease after Adriamycin-induced podocyte injury, as demonstrated by worsened glomerular scarring, increased podocyte foot process effacement and podocyte loss. There was a decrease in PAX2-expressing PECs in wild type mice after Adriamycin injury accompanied by the occurrence of PAX2/WT-1 co-expressing glomerular tuft cells. In contrast, Pax2A220G/+ mice showed no changes in the numbers of PAX2-expressing PECs after Adriamycin injury, associated with fewer PAX2/WT-1 co-expressing glomerular tuft cells compared to injured wild type mice. A subset of PAX2 expressing glomerular tuft cells after Adriamycin injury was increased in Pax2A220G/+ mice, suggesting a pathologic process given the worse outcomes observed in this group. Lastly, Pax2A220G/+ mice h...

Source: Am J Physiol Renal P... - March 14, 2024 Category: Urology & Nephrology Authors: Joanna Cunanan Sarada Sriya Rajyam Bedra Sharif Khalil Udwan Akanchaya Rana Vanessa De Gregorio Samantha Ricardo Andrew Elia Brian Brooks Astrid Weins Martin Pollak Rohan John Moumita Barua Source Type: research