Abstract: FR-PO366
Klotho Restrains RIG-1/NF-κB Signaling Activation and Monocyte Inflammatory Factor Release Under Uremic Conditions
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Author
- He, Ting, Xinqiao Hospital, Chongqing, Chongqing, China
Background
Systemic inflammation is a main hallmark of chronic kidney disease (CKD). However, the mechanisms underlying the pathogenesis of CKD-associated systemic inflammation are unclear. Our study aimed to investigate the relationship between indoxyl sulphate (IS) and CKD-associated systemic inflammation, and the protective effect of Klotho against IS-induced systemic inflammation in CKD.
Methods
Serum Klotho was measured by ELISA. Heterozygous kl/kl (kl/+) mice or WT mice were treated with 5/6 renal damage and then injected with recombinant Klotho protein.
Results
It shows that in 286 CKD patients, the serum levels of inflammatory factors are positively related with IS, but negatively related with Klotho. Klotho can significantly inhibit IS-induced retinoic acid-inducible gene I (RIG-I) /NF-κB activation and the productions of IL-6 and TNF-α in cultured monocytes. In vivo, RIG-I/NF-κB activation is observed in monocytes in both CKD mice and patients. Notably, higher levels of IL-6 and TNF-α are detected in kl+/- mice with CKD. Klotho administration can evidently attenuate RIG-I/NF-κB activation in monocytes and systemic inflammation in CKD mice.
Conclusion
These results suggest that Klotho can suppress CKD-associated systemic inflammation through inhibiting IS-induced RIG-1/NF-κB activation and monocyte inflammatory factor release.
The basic information of 286 CKD patients
| CKD stage | CKD 2（n=36） | CKD 3（n=51） | CKD 4（n=55） | CKD 5（n=144） | P |
| Age, years | 39.86±11.9 | 49.88±13.88 | 47.27±14.89 | 46.29±14.18 | ＜0.05 |
| Male gender, n(%) | 19(53) | 22(43) | 34(62) | 60(42) | ＜0.001 |
| eGFR（ml/min/1.73m2） | 71.16(67.41,82.22) | 42.79(36.04,53.27) | 19.71(16.99,25.22) | 8.14(6.39,10.45) | ＜0.001 |
| BMI（kg/m2） | 24.06±2.89 | 24.50±3.50 | 23.23±2.99 | 22.34±3.43 | ＜0.001 |
| ALB（g/L） | 41.50(34.43,45.28) | 39.00(35.30,42.40) | 40.40(35.30,43.80) | 38.85(36.40,42.08) | ＞0.05 |
| Uric acid（μmol/L） | 434.50±90.46 | 429.24±94.02 | 500.60±113.53 | 539.04±123.22 | ＜0.001 |
Klotho inhibits IS-induced monocyte activation by restraining RIG-1/ NF-κB signaling