1. IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.
- Author
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Jiafa Ren, Xiaohan Lu, Hall, Gentzon, Privratsky, Jamie R., Robson, Matthew J., Blakely, Randy D., and Crowley, Steven D.
- Subjects
KIDNEY glomerulus diseases ,INTERLEUKIN-1 ,KIDNEY injuries ,DIABETIC nephropathies ,ALBUMINURIA ,CELLULAR signal transduction - Abstract
Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in podocytes, we selectively ablated podocyte IL-1R1 in mice (PKO mice). We then subjected PKO mice and wild-type controls to two glomerular injury models: nephrotoxic serum (NTS)- and adriamycin-induced nephropathy. Surprisingly, we found that IL-1R1 activation in podocytes limited albuminuria and podocyte injury during NTS- and adriamycin-induced nephropathy. Moreover, deletion of IL-1R1 in podocytes drove podocyte apoptosis and glomerular injury through diminishing Akt activation. Activation of Akt signaling abrogated the differences in albuminuria and podocyte injury between wild-type and PKO mice during NTS. Thus, IL-1R1 signaling in podocytes limits susceptibility to glomerular injury via an Akt-dependent signaling pathway. These data identify an unexpected protective role for IL-1R1 signaling in podocytes in the pathogenesis of glomerular disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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