Abstract: TH-PO356

Toll-Like Receptor 8 and 10 Are Possibly Associated with Pathogenic Mechanisms of Idiopathic Nephrotic Syndrome

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Tanaka, Eriko, Tokyo Medical and Dental University, Tokyo, Japan
  • Takagi, Miyuki, Division of Nephrology, Tokyo, Japan
Background

Idiopathic nephrotic syndrome (ISN) is still a disease of unknown cause, though many studies have been done to elucidate pathogenic mechanisms. Some studies suggest that disorder of immune system derived by toll-like receptor (TLR) is involved, however, expressions of TLRs in ISN patients are not fully examined.

Methods

We investigated RNA expressions of TLRs and its pathways in ISN patients. Total RNA was extracted from kidney biopsy specimens of each ISN patients. We performed RNA-sequencing and analyzed RNA expressions of TLRs and molecules related to TLR pathways.

Results

Three patients with ISN were enrolled in this study (P1, P2, and P3). At the time of kidney biopsy, proteinuria of P1 was decreasing and she achieved remission a few days after the biopsy. P2 and P3 had nephrotic range of proteinuria when they received kidney biopsy. Pathological diagnosis of both P1 and P2 was minor glomerular abnormality, while that of P3 was focal segmental glomerulosclerosis. We analyzed RNA expressions of patients and found that TLR 8 and TLR 10 were significantly low in P1 compared to those in P2 and P3. (Fold Change (FC) of P1 vs P2 and P1 vs P3 in TLR8 were -6.59 and -4.62, respectively, and FC in TLR10 were -25.38 and -40.03, respectively.) RNA expressions in TLR1, 2, 3, 4 and 9 showed no differences among the three patients. We explored the molecules in pathway of TLR8 and found that IRF7 and IRAK2, which are the downstream molecules leading to type 1 interferon activation, are significantly low in P1 in comparison to those in P2 and P3. We next investigated expressions of molecules related to TLR10. On contrary to previous reports, RNA expressions of pro-inflammatory cytokines such as IL1β and IL-6 were significantly low in P1 who showed lower expression of TLR10, suggesting that TLR10 expression was secondary suppressed because of activation of pro-inflammatory cytokines.

Conclusion

The profile of RNA expressions in INS patients implies the possibility of TLR pathways’ involvement in pathogenic mechanisms. Comparing the RNA expressions in INS patient in remission phase to INS patient in nephrotic phase revealed that pathways related to TLR8 and TLR10 may be associated with onset and remission of INS.

Funding

  • Private Foundation Support