IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.

Journal Article (Journal Article)

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.NEW & NOTEWORTHY The present study establishes that activation of the receptor for interleukin-1 limits susceptibility to damage to the kidney glomerulus in preclinical mouse models by stimulating Akt signaling cascades inside the podocyte.

Full Text

Duke Authors

Cited Authors

  • Ren, J; Lu, X; Hall, G; Privratsky, JR; Robson, MJ; Blakely, RD; Crowley, SD

Published Date

  • February 1, 2022

Published In

Volume / Issue

  • 322 / 2

Start / End Page

  • F164 - F174

PubMed ID

  • 34894725

Pubmed Central ID

  • PMC8782651

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00353.2021


  • eng

Conference Location

  • United States