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

Publication ,  Journal Article
Ren, J; Lu, X; Hall, G; Privratsky, JR; Robson, MJ; Blakely, RD; Crowley, SD
Published in: Am J Physiol Renal Physiol
February 1, 2022

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.

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Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

February 1, 2022

Volume

322

Issue

2

Start / End Page

F164 / F174

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Interleukin-1 Type I
  • Proto-Oncogene Proteins c-akt
  • Proteinuria
  • Podocytes
  • Mice, Knockout
  • Mice, 129 Strain
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
 

Citation

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Ren, J., Lu, X., Hall, G., Privratsky, J. R., Robson, M. J., Blakely, R. D., & Crowley, S. D. (2022). IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage. Am J Physiol Renal Physiol, 322(2), F164–F174. https://doi.org/10.1152/ajprenal.00353.2021
Ren, Jiafa, Xiaohan Lu, Gentzon Hall, Jamie R. Privratsky, Matthew J. Robson, Randy D. Blakely, and Steven D. Crowley. “IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.Am J Physiol Renal Physiol 322, no. 2 (February 1, 2022): F164–74. https://doi.org/10.1152/ajprenal.00353.2021.
Ren J, Lu X, Hall G, Privratsky JR, Robson MJ, Blakely RD, et al. IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage. Am J Physiol Renal Physiol. 2022 Feb 1;322(2):F164–74.
Ren, Jiafa, et al. “IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.Am J Physiol Renal Physiol, vol. 322, no. 2, Feb. 2022, pp. F164–74. Pubmed, doi:10.1152/ajprenal.00353.2021.
Ren J, Lu X, Hall G, Privratsky JR, Robson MJ, Blakely RD, Crowley SD. IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage. Am J Physiol Renal Physiol. 2022 Feb 1;322(2):F164–F174.

Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

February 1, 2022

Volume

322

Issue

2

Start / End Page

F164 / F174

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Interleukin-1 Type I
  • Proto-Oncogene Proteins c-akt
  • Proteinuria
  • Podocytes
  • Mice, Knockout
  • Mice, 129 Strain
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins