MicroRNA-223 downregulation promotes HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome

Yani Yu1, Hui Dong2, Yue Zhang3

  • 1Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China.

Archives of Virology
|June 22, 2022
PubMed

Insights

MicroRNA-223 (miR-223) downregulation promotes podocyte pyroptosis in Hepatitis B virus X (HBx)-associated kidney disease. Restoring miR-223 levels may offer a therapeutic strategy for Hepatitis B virus-associated glomerulonephritis (HBV-GN).

Area of Science:

  • Nephrology
  • Molecular Biology
  • Virology

Background:

  • Hepatitis B virus X protein (HBx) contributes to podocyte injury in Hepatitis B virus-associated glomerulonephritis (HBV-GN).
  • The NLRP3 inflammasome mediates pyroptosis, a form of programmed cell death, and is implicated in kidney diseases.
  • MicroRNA-223 (miR-223) is involved in various disease processes, including those related to Hepatitis B virus (HBV).

Purpose of the Study:

  • To investigate the role and mechanism of miR-223 in HBx-induced podocyte pyroptosis.
  • To determine if miR-223 targets the NLRP3 inflammasome pathway in this context.

Main Methods:

  • Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) to assess miR-223 expression.
  • Transfection of podocytes with miR-223 mimics, miR-223 inhibitors, HBx, and NLRP3 overexpression plasmids.
  • Analysis of NLRP3 inflammasome components and pyroptosis-related proteins.

Main Results:

  • miR-223 was found to be downregulated in HBx-transfected podocytes.
  • Overexpression of miR-223 suppressed NLRP3 inflammasome activation and subsequent cytokine release.
  • Inhibition of miR-223 exacerbated HBx and NLRP3-induced pyroptosis.

Conclusions:

  • Downregulation of miR-223 is a key factor in HBx-induced podocyte pyroptosis via targeting the NLRP3 inflammasome.
  • miR-223 represents a potential therapeutic target for mitigating inflammation in HBV-associated glomerulonephritis (HBV-GN).