• Original article (Basic research) • Previous Articles     Next Articles

Effect of activating PKA signaling on dedifferentiation of podocytes in adriamycin-induced nephropathy mice

JIANG Jin-xing1, XIANG Peng1, CHEN Xiao-huan2, AYIJIAKEN Kasimumali2, XIE Ke-wei1, NI Zhao-hui1, GU Le-yi1   

  1. 1. Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2. Department of Nephrology, Second People's Hospital of Kashi, Xinjiang Uygur Autonomous Region, Kashi 844099, China
  • Online:2017-04-28 Published:2017-05-04
  • Supported by:

    Natural Science Foundation of Xinjiang Uygur Autonomous Region, 2015211C222

Abstract:

Objective · To explore effects of pCPT-cAMP on proteinuria and dedifferentiation of podocytes in adriamycin (ADR)-induced nephropathy mice. Methods · Male BALB/c mice were divided into three groups. The control group did not make any intervention, and the other mice were administrated with ADR in a dose of 10 mg/kg by intravenous injection (ADR group). Some ADR-injected mice were treated with pCPT-cAMP [50 mg/(kg·d)] by intraperitoneal injection everyday (A+P group). Albumin urine was detected by Coomassie blue stain. Urine creatinine concentration was estimated by ELISA. The expression of WT-1 was detected by immunohistochemical staining. Immunofluorescence staining and Western blotting were used to evulate the dedifferentiation of podocytes. Results · Compared with the control group, the ratio of urinary albumin/creatinine in ADR nephropathy mice was significantly increased. WT-1 immunohistochemical staining showed that the number of podocytes was significantly decreased, while immunofluorescence double staining of podocyte-specific protein synaptopodin and podocalyxin remarkably reduced, and the expression of desmin was increased. pCPT-cAMP intervention decreased the ratio of albumin/creatinine in ADR mice, elevated the quantity of WT-1 positive cells and the expression of synaptopodin and podocalyxin, while desmin expression decreased. Conclusion · pCPT-cAMP activates the PKA signaling and protects ADR nephropathy mice by preventing the loss of podocytes and ameliorating the urine albumin/creatinine ratio, which may be mediated by pCPT-cAMPprevented dedifferentiation of podocytes.

Key words: protein kinase A, podocyte, dedifferentiation, adriamycin