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Abstract: TH-PO525

Total Flavonoids of Astragalus Ameliorates Renal Injury-Related Mineral and Bone Metabolic Disorder in the CKD-MBD Model Rats by Regulating FGF23-Klotho Signaling Axis, Compared with Calcitriol

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
  • Liu, Buhui, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China

Group or Team Name

  • Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
Background

Recently, chronic kidney disease-mineral and bone disorder (CKD-MBD) has become one of serious complications occurring in the CKD patients. Hence, the development of a new treatment for CKD-MBD is very important in clinics. FGF23-Klotho signaling axis is a pivotal regulator of MBD in the CKD-MBD patients. Targeting FGF23-Klotho signaling axis in response to renal injury-related MBD has been thereby identified as the multi-targets in the treatment of CKD-MBD. In China, total flavonoids in the flower of Abelmoschus manihot (TFA), a natural extract has been frequently used to improve renal dysfunction in the CKD patients. But the potential mechanisms in vivo of TFA on renal injury-related MBD remained unclear. Here, we verified whether TFA could ameliorate renal injury-related MBD in the CKD-MBD model rats by targeting FGF23-Klotho signaling axis in the kidney, compared to calcitriol (CAL).

Methods

Twenty-eight rats were divided into 4 groups, the Sham, the Vehicle, the TFA and the CAL groups. The appropriate doses of TFA, CAL and distilled water were administrated with oral for 3 weeks after the induction of CKD-MBD by adenine-administration and mononephrectomy, respectively. The changes in parameters of renal injury and bone abnormality in urine, blood, bone and kidneys were analyzed. The kidney and femur bone were isolated for histomorphometry, immunohistochemistry and Western blot at sacrifice.

Results

For the CKD-MBD model rats, renal injury and bone abnormality were significantly revealed, and there was a potential connection between renal injury and bone abnormality. Moreover, TFA alleviated renal dysfunction and tubulointerstitial pathological changes, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi2α pathway in the kidney. Notably these beneficial actions in vivo of TFA were markedly different from CAL.

Conclusion

We clarified that TFA, different from CAL, can improve renal injury and bone abnormality, and that, more importantly, these ameliorative effects on renal injury-related MBD are closely associated with the regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi2α pathway in the kidney. This study provided the first evidence that TFA directly contributes to the prevention of CKD-MBD.

Funding

  • Government Support - Non-U.S.