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Abstract: TH-PO179

The Characteristics and Mechanism of Cell Senescence in Patients With Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Zhang, Ying, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
  • Zhu, Xiaodong, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
  • Zhang, Xiaoliang, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
  • Zhao, Yu, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
Background

Cellular senescence commonly occurs in renal innate cells of diabetic kidney disease (DKD) and autophagy may be involved. However, the features of senescent cells in different pathological stages of DKD, as well as the driving force behind cell senescence remain unknown. The study aims to investigate the characteristics of cell senescence in renal tissue during different pathological stages of DKD and their relationship with renal function and the role of autophagy in it.

Methods

Fifty DKD patients diagnosed by renal biopsy were divided into I IIa IIb III IV classes according to the pathologic typing. The other six normal kidney specimens taken from patients with renal trauma or tumor were as the control group. Serum creatinine and proteinuria were collected. Pathological changes in kidney were detected by PAS staining, and the expression of senescence marker p21 was demonstrated by immunohistochemistry. DKD rats were established by intraperitoneal injection with streptozotocin (STZ) and sacrificed respectively at 14w. HK-2 cells were cultured with 25mM glucose with or without autophagy inhibitor (chloroquine (CQ)) and activator (rapamycin). The expressions of LC3, p62(autophagy proteins)and p53,p21(senescence markers)were detected by immunohistochemistry and Western Blot.

Results

In kidney biopsies, the p21 expression was increased in interstitium and tubules and tightly associated with disease progression(p<0.05), which was proportional to the degree of deterioration of renal function. Similar trends were also observed in the levels of p21, p53, p62 and LC3 in DKD groups (p<0.05). Electronic microscope showed an increase in autophagosomes in the renal tubules of DKD rats.HK-2 cells treated with high glucose exhibited increased expression of p21, p53, p62 and LC3(p<0.05).CQ elevated p21 and p53 compared to the high glucose group, whereas opposite trend was observed in the rapamycin treatment (p<0.05).

Conclusion

Our study demonstrated a positive correlation between cell senescence and progression of DKD, and autophagy attenuated the high-glucose-mediated renal tubule senescence.