Abstract: FR-PO412
The Possible Mechanisms of Effects of NF-κB Inhibitor Parthenolide on Promoting Renal Tubules Albumin Reabsorption in Type 2 Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Hao, Qiufa, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China, Beijing, China. , Beijing, BeiJIng, China
- Li, Xuemei, Peking Union Medical College Hospital, Beijing, BEIJING, China
Background
Increased albuminuria caused by albumin reabsorption reduction of renal tubules is highlighted as the cause of early stage of diabetic nephropathy. The underlying mechanism has not been fully figured out. We aimed to observe whether reducing inflammation thereby remodeling impaired insulin signaling could improve renal tubules albumin uptake in diabetic nephropathy.
Methods
1)8-weeks db/m and db/db mice were used as control(C group) and diabetic nephropathy model(DN group). Parthenolide(PTN 1mg/kg) was used intraperitoneally every other day to db/db mice as treatment group(DN+PTN group). After 8-weeks treatment, urine, blood and kidney samples were collected. Expressions of NF-κB, insulin signaling protein pAKT/AKT and albumin receptors amnionless(AMN) and cubilin in kidneys were detected by immunohistochemistry and immunoblotting.
2)HKC cells were treated with TNF-α(25ng/ml), PTN(5μM) and insulin(100nM). Albumin uptake and expressions of NF-κB, pAKT/AKT, AMN and cubilin were tested by fluorometric assay and immunoblotting.
Results
1)Compared with DN group, DN+PTN group showed decreased insulin resistance index levels(P<0.05) and slightly reduced urine albumin creatinine ratio levels(P>0.05).
2)NF-κB expression increased and phosphorylation of AKT decreased in DN group compared with C group (P<0.05). PTN reduced NF-κB expression and ameliorated decline of AKT phosphorylation(P<0.05). Compared with C group, AMN and cubilin expressions decreased in DN group(P<0.05), and PTN attenuated reduction of cubilin expression(P<0.05).
3)Insulin promoted AMN and cubilin expressions and albumin uptake of HKC cells(P<0.05). In TNF-α group, NF-κB expression increased and AKT phosphorylation decreased compared with insulin group(P<0.05). In TNF-α+PTN group, PTN reduced NF-κB expression and AKT phosphorylation(P<0.05). AMN and cubilin expressions decreased in TNF-α group(P<0.05), and PTN attenuated reduction of cubilin expression(P<0.05).
Conclusion
The study observed in diabetic nephropathy PTN could ameliorate insulin resistance and slightly reduce albuminuria. We found albuminuria with albumin receptors reduction was induced by inflammation impaired insulin signaling in renal tubules. PTN could reduce inflammation, remodel impaired insulin signaling, and then increase albumin uptake by ameliorating albumin receptors expressions.