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Abstract: TH-PO878

Hyperoside Alleviates the Early Glomerular Pathological Changes in Diabetic Kidney Disease by Inhibiting Akt/mTOR/p70S6K Signaling Activity

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Wu, Wei, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
  • Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
Background

Hyperoside (HYP), a bioactive component of Abelmoschus manihot, has been widely applied to clinical therapy in the early diabetic kidney disease (DKD) patients. However, it remains elusive whether HYP can ameliorate inchoate glomerular injuries in hyperglycemia. Recently the activation of phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling and its downstream regulator, 70-kDa ribosomal protein S6 kinase (p70S6K), play important roles in the early glomerular pathological changes of DKD including glomerular hypertrophy, glomerular basement membrane (GBM) thickening and mild mesangial expansion. This study aimed to clarify therapeutic effects of HYP during the initial phase of DKD and its underlying mechanisms.

Methods

Fifteen rats were randomly divided into 3 groups: the normal, the model and the HYP groups. The early DKD model rats were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with either HYP suspension or vehicle after modeling and for a period of 4 weeks. Changes in incipient glomerular lesions-related parameters in urine and blood were analyzed. Kidneys were isolated for histomorphometry, immunohistochemistry, immunofluorescence and Western blotting (WB) at sacrifice. In vitro, murine mesangial cells (MCs) were used to investigate inhibitory actions of HYP, on cellular hypertrophy-associated signaling pathway by WB, compared with rapamycin (RAP).

Results

For the early DKD model rats, HYP ameliorated micro-urinary albumin, body weight and serum albumin, but had no significant effects on renal function and liver enzymes; HYP improved renal shape, kidney weight and kidney hypertrophy index; HYP attenuated glomerular hypertrophy, GBM thickening and mild mesangial expansion; HYP inhibited phosphorylation of Akt, mTOR and p70S6K, and protein over-expression of transforming growth factor-β1 in kidneys. In vitro, phosphorylation of PI3K, Akt, mTOR and p70S6K in MCs induced by high-glucose was abrogated by treatment of HYP or RAP.

Conclusion

This study demonstrated HYP alleviates the early glomerular pathological changes of DKD, likely by inhibiting Akt/mTOR/p70S6K signaling activity in vivo and in vitro, and provided the first evidence that HYP directly contributes to the prevention of the early DKD.

Funding

  • Government Support - Non-U.S.