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Abstract: TH-PO189

Role of Toll-like Receptors in Hyperglycemia Induced Injury in Proximal Tubules and Podocytes

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Upadhyay, Rohit, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Bhargava, Rhea, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Batuman, Vecihi, Tulane University School of Medicine, New Orleans, Louisiana, United States
Background

Diabetic kidney disease (DKD) is a progressive microvascular complication of diabetes mellitus where hyperglycemia induces injury in proximal tubules as well as podocytes and eventually develops in to end-stage renal disease (ESRD). The dysregulated metabolic environment mimicking hyperglycemia initiates DKD. Toll like receptors (TLRs) are first line of defense in innate immunity; however, the role of TLRs in hyperglycemia induced injury in proximal tubules and podocytes has not been well understood.

Methods

Human kidney proximal tubule cells (PTCs; HK2 cell line) and human podocytes were exposed to high glucose media at different time points in vitro. Cell proliferation, ROS generation, NO production, m-RNA/ protein expressions and mitochondrial dysfunction was checked in the cells after treating them with high glucose.

Results

We identified a differential role of TLRs in PTCs and podocytes. TLRs 2, 3, 4, 6 and 9 were activated in PTCs and podocytes cultured in high glucose media. SIRT1 downregulation was correlated with expression of cell specific injury markers (LCN2 for PTCs and SYNPO for podocytes). NLRP3 was activated at late time points; however, TNFA was identified as most prominent upregulated cytokine in time dependent manner for both cell types.

Conclusion

TLRs-TNFA-NLRP3 axis mediated injury to PTCs and podocytes could be a novel mechanism and promising target to treat DKD.