Abstract: SA-PO496
TNF-α Inhibition Protects Against Renal Tubulointerstitial Injury Associated with Suppressing NLRP3 Inflammasome in Diabetic Rats
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Wang, Feng, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Yin, Jianyong, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Zhao, Ting, Shanghai Sixth People''s Hospital, Shanghai, China
- Kong, Yiwei, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Liu, Xuanchen, Shanghai Jiao Tong University Afflicted Sixth People's Hospital, Shanghai, SHANGHAI, China
Background
Tubular injury exerts a pivotal role in the development of diabetic nephropathy (DN), but current therapies used to treat DN do not combat tubular injury. This study was conducted to investigate whether TNF-α inhibition protected against tubular injury in diabetic rats and examine the associated mechanisms.
Methods
Kidney biopsy tissues, taken from twelve patients with DN and five control subjects, were analyzed. STZ-induced diabetic rats were treated with a TNF-α inhibitor (Humira) for twelve weeks. Renal function, albuminuria, histological injury, renal TNF-α mRNA, and NLRP3 inflammasome was assessed.
Results
Diabetic patients with tubulointerstitial injury presented with higher renal tubular expression of TNF-α mRNA and NLRP3 inflammasome. TNF-α inhibition reduced albuminuria, glomerular injury, and tubular injury in STZ-induced diabetic rats. Importantly, TNF-α inhibition significantly reduced NLRP3 inflammasome in tubules. Moreover, TNF-α inhibition decreased expression of tubular IL-6 and IL-17A, which could activate NLRP3 inflammasome.
Conclusion
TNF-α inhibitor can protect against tubulointerstitial injury associated with suppressing NLRP3 inflammasome in diabetic rats.