Abstract: SA-PO124
A1AR Alleviates Tubulo-Interstitial Fibrosis by Inhibiting Peritubular Capillary Loss in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - III
October 27, 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
- Tian, Dongli, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Shi, Xiaoxiao, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Peng, Xiaoyan, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Ma, Ying, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Xia, Peng, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Wen, Yubing, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Chen, Limeng, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
Background
We previously observed A1 adenosine receptor (A1AR) had a protective role in the progression of diabetic nephropathy. But the mechanism was not clear. The disintegration of interstitial pericytes may cause peritubular capillary(PTC) loss and interstitial fibrosis.In this study, we used A1AR deficient diabetic mice to prove whether A1AR plays a role in the pericyte detachment mediated PTC loss and in the progress of renal interstitial fibrosis.
Methods
Eight week-old male C57BL/6J A1AR-/- and WT mice were given two consecutive days' intraperitoneal injection streptozotocin to establish type 1 diabetic nephropathy mice. At 4w and 16w for modeling, mice were sacrificed to collect blood, urine and kidney samples for intensive detection.
Results
We successfully established streptozotocin induced type 1 diabetic nephropathy model in WT and A1AR deficient mice.At 4 weeks,albuminuria and mild renal pathological leisure were observed in WT diabetic mice, with up-regulation of A1AR protein expression (1.3times, P=0.042). At 16weeks, more serious albuminuria and renal pathological leisure were observed in WT diabetic mice than at 4weeks, along with pericyte detachment induced platelet-derived growth factor receptor (PDGFR) activation(1.3times, P=0.023) and peritubular capillary injury(CD34 staining). While in A1AR-/- diabetic mice, severer renal tubular interstitial fibrosis and increased pre-clollagen I expression(1.8times, P<0.001 ) were observed than in WT diabetic mice,along with activation of inflammation,including increased inflammasome nod -like receptor protein 3 (NLRP3, 2.0 times, P=0.006),and it’s downstream proinflammatory cytokine IL-1β. Meanwhile more increased protein expression of PDGFR (1.4times, P=0.008) and PTC lost (1.3times, P=0.016) were detected by immunohistochemistry and western-blot.
Conclusion
A1AR plays a protective role in the PDGFR-mediated peritubular capillary loss to alleviate renal tubular interstitial fibrosis in type 1 diabetic nephropathy.