by Researchers from the University of Houston, Texas A&M University, and the University of California Riverside have recently published a study titled “Contribution of Membrane Raft Redox Signaling to Visfatin-Induced Inflammasome Activation and Podocyte Injury,” shedding light on the mechanism through which obesity increases the advancement of chronic kidney disease. The researchers found that adipokine visfatin-induced NLRP3 inflammasome activation contributes to podocyte injury.
Obesity has become a significant health concern worldwide as it increases the risk of chronic kidney diseases such as diabetes and hypertension, which can eventually lead to chronic kidney disease or end-stage renal disease. However, the exact mechanism behind how obesity accelerates chronic kidney disease remains unknown.
To investigate this, the researchers focused on understanding how visfatin, an adipokine, induces NLRP3 inflammasome activation and podocyte damage. They hypothesized that the membrane raft (MR) redox signaling pathway plays a central role in this process.
The study found that upon visfatin stimulation, NADPH oxidase subunits (gp91phox and p47phox) aggregated in the MR clusters of podocytes, forming an MR redox signaling platform. This signaling platform was blocked by pre-treatment with the MR disruptor MCD or the NADPH oxidase inhibitor DPI. Additionally, visfatin stimulation increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1, leading to IL-β production, cell permeability, and podocyte damage.
The researchers also observed that pretreatment with MCD, DPI, and WEHD significantly abolished the visfatin-induced colocalization and production of IL-1β, as well as the podocyte damage. Furthermore, immunofluorescence analysis revealed that visfatin treatment reduced the expression of podocin and nephrin, which are markers of podocyte damage.
In conclusion, the study suggests that visfatin stimulates the clustering of membrane rafts in podocyte membranes, forming redox signaling platforms through the aggregation and activation of NADPH oxidase subunits. This enhances the production of reactive oxygen species, leading to NLRP3 inflammasome activation and subsequent podocyte injury.
The researchers highlight that this study provides the first evidence that membrane raft-associated redox signaling is crucial for NLRP3 inflammasome assembly and activation in response to visfatin, ultimately resulting in podocyte dysfunction and injury. These findings contribute to a better understanding of inflammasome activation and podocyte injury caused by visfatin, offering potential avenues for future therapeutic interventions.
The study was published in the journal Aging and identifies a novel mechanism underlying the progression of chronic kidney disease in obese individuals. By deciphering the molecular pathways involved in visfatin-induced inflammation and kidney damage, researchers can develop targeted treatments that mitigate these effects and potentially improve the prognosis for patients with obesity-related chronic kidney diseases.
The researchers hope that further investigation into the molecular mechanisms involved in obesity-related kidney damage will provide a basis for developing effective therapeutic strategies to prevent or delay the progression of chronic kidney disease in obese patients.
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1. Source: Coherent Market Insights, Public sources, Desk research
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