Abstract: SA-PO136
Tubulointerstitial Injury in Renal Congestion Was Suppressed by Inhibiting Platelet-Derived Growth Factor Pathway
Session Information
- AKI: Mechanisms - AKI-CKD Transition
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Matsuki, Takuma, Tohoku Univeristy, Sendai, Japan
- Hirose, Takuo, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- Takahashi, Chika, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- Mori, Takefumi, Tohoku Medical and Pharmaceutical University, Sendai, Japan
Background
Increased central venous pressure in congestive heart failure is responsible for renal dysfunction. We created a novel rat renal congestion model, resulting high renal interstitial hydrostatic pressure, tubulointerstitial injury and pericyte-myofibroblast transition (PMT). In this model, platelet-derived growth factor receptors (PDGFRs), PMT indicators, were also upregulated, especially in outer medulla. Thus we examined the effect of imatinib, a PDGFR inhibitor, for renal injury.
Methods
The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawly rats to increase upstream IVC pressure and induce congestion in the left kidney only. Imatinib mesylate (20 mg/kg) or saline were injected intraperitoneally every day from one day of the operation. Both control right kidney and congesitve left kidney were obtained after 3 days of the surgery and were weighted. The expression of renal injury marker and PDGFRs were assessed by quantitative reverse transcription-polymerase chain reaction, western blot and immunohistochemistry.
Results
Kidney weight was significantly increased in left congestive kidney, and ameliorated by imatinib administration. Staining intensity and mRNA expression levels of Tagln, Pdgfra, Pdgfrb were higher in the control kidneys, especially in the cortex. Imatinib attenuated the intensity and mRNA expression levels. Fibronectin and Kim1 expression was higher in the control kidneys and were attenuated by imatinib.
Conclusion
Imatinib attenuates the elevation of kidney weight and PMT markers. These results suggest that imatinib has potentiality against renal fibrosis in renal congestion.
Funding
- Private Foundation Support