Podocyte NLRP3 Inflammasome Activation and Formation by Adipokine Visfatin. Academic Article uri icon


  • BACKGROUND/AIMS: NLRP3 inflammasome activation has been reported to be an early mechanism responsible for glomerular inflammation and injury in obese mice. However, the precise mechanism of obesity-induced NLRP3 inflammasome activation remains unknown. The present study explored whether adipokine visfatin mediates obesity-induced NLRP3 inflammasome activation and consequent podocyte injury. METHODS: Inflammasome formation and immunofluorescence expressions were quantified by confocal microscopy. Caspase-activity, IL-1 production and VEGF concentrations were measured by ELISA. RESULTS: Confocal microscopic analysis showed that visfatin treatment increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1 in podocytes indicating the formation of NLRP3 inflammasomes. This visfatin-induced NLRP3 inflammasome formation was abolished by pretreatment of podocytes with Asc siRNA. Correspondingly, visfatin treatment significantly increased the caspase-1 activity and IL-1 production in podocytes, which was significantly attenuated by Asc siRNA transfection. Further RT-PCR and confocal microscopic analysis demonstrated that visfatin treatment significantly decreased the podocin expression (podocyte damage). Podocytes pretreatment with Asc siRNA or caspase-1 inhibitor, WEHD attenuated this visfatin-induced podocin reduction. Furthermore, Asc siRNA transfection was found to preserve podocyte morphology by maintaining the distinct arrangement of F-actin fibers normally lost in response to visfatin. It also prevented podocyte dysfunction by restoring visfatin-induced suppression of VEGF production and secretion. CONCLUSION: Visfatin induces NLRP3 inflammasome activation in podocytes and thereby resulting in podocyte injury.

published proceedings

  • Cell Physiol Biochem

altmetric score

  • 5.08

author list (cited authors)

  • Koka, S., Xia, M., Zhang, C., Zhang, Y., Li, P., & Boini, K. M.

citation count

  • 9

complete list of authors

  • Koka, Saisudha||Xia, Min||Zhang, Chun||Zhang, Yang||Li, Pin-Lan||Boini, Krishna M

publication date

  • January 2019