Abstract: TH-PO979
Ionizing Radiation Could Cause Cellular Senescence in Kidney and Late-Onset Kidney Dysfunction - Experiment Using Radiation Nephropathy Rat Model
Session Information
- Pathology and Lab Medicine: Basic
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1501 Pathology and Lab Medicine: Basic
Authors
- Aratani, Sae, Nippon Medical School Hospital, Tokyo, Japan
- Tagawa, Masako, Nippon Medical School, Tokyo, Japan
- Nagasaka, Shinya, Nippon Medical School, Tokyo, Japan
- Sakai, Yukinao, Nippon Medical School Hospital, Tokyo, Japan
- Shimizu, Akira, Nippon Medical School, Tokyo, Japan
- Tsuruoka, Shuichi, Nippon Medical School, Tokyo, Japan
Background
Cellular senescence is one of the major risk factors for chronic kidney disease. Cellular senescence is caused by a variety of stressors, such as ionizing radiation (IR). The kidney is known as radiosensitive organ, however the association between cellular senescence and kidney dysfunction is still unclear.
Methods
7-8-week-old male rats received unilateral IR of 18 Gy on the left or right kidney (irradiated kidney) whereas normal rats received sham IR (normal kidney). We compared the presence of cellular senescence, kidney dysfunction, and pathological changes at 9 months after the IR. Cellular senescence was defined by positive staining for SA-β-gal and p21, increased mRNA expression level of p21, and senescence associated secretory phenotype (IL-6). Pathological evaluation was performed focusing on glomerular findings, which were evaluated in 50 glomeruli. Endothelial cell was detected by CD31 staining. We also confirmed the endothelial senescence by vitro fashion with rat cultured endothelial cells received IR of 20 Gy with 25 days culturing.
Results
As shown in Table, markers of cellular senescence were elevated only in irradiated kidney. Regarding kidney dysfunction, irradiated rats showed higher proteinuria, and greater serum level of BUN. Pathological findings suggested strong endothelial cell injury in irradiated kidney with greater TMA and collapsing glomeruli, and reduced endothelial cell numbers. We confirmed endothelial cell senescence in vitro model, showing increased positive staining for SA-β-gal, expression level of p21 and IL-6.
Conclusion
Taken together, these data suggested IR could cause cellular senescence in the kidney and lead to resultant kidney dysfunction. The cellular senescence of glomerular endothelial cells may be associated with TMA and glomerular collapse, that lead to kidney dysfunction.