Tripterygium glycoside protects diabetic kidney disease mouse serum-induced podocyte injury by upregulating autophagy and downregulating β-arrestin-1
2019
Background. Diabetic kidney disease (DKD),
one of the most common causes of end-stage renal
disease (ESRD), remains prevalent in many populations.
Podocyte loss and apoptosis play a crucial role in the
progression of DKD. Tripterygium glycoside (TG), a
widely used Chinese herb, exerted comprehensive
protective effects on preventing DKD progression. This
study was performed to assess the podocyte protective
effect of tripterygium glycoside on DKD by the potential
role of activation of autophagy and downregulating β-
arrestin-1.
Methods. Tripterygium glycoside and small
interfering RNA (siRNA) of β-arrestin-1 were added to
10% db/db mice high-glucose serum induced podocytes
in vitro. Autophagic activity was evaluated by
transmission electronic microscopy, immunofluorescence
staining and western blot analysis.
Apoptotic activity was evaluated by Annexin V-FITC/PI
flow cytometric analysis. The levels of nephrin and
podocin, a marker protein of podocytes, were examined
using western blot analysis.
Results. Significantly ameliorated podocyte
apoptosis, increased nephrin and podocin levels and
inhibited expression of β-arrestin-1 were observed after
pretreatment of tripterygium glycoside in DKD mouse
serum treated podocytes. Significantly higher levels of
autophagic activity were also observed. Silencing β-
arrestin-1 upregulated autophagic activity and
ameliorated podocyte apoptosis. Silencing β-arrestin-1
in combination with tripterygium glycoside enhanced the
levels of LC3-II and LC3-II/LC3-I ratios and reduced
the expression of p62. Finally, we observed a notable
reduction in podocyte apoptotic rate in DKD serum +
siRNA-β-arrestin-1 + TG group compared to DKD
serum + siRNA-β-arrestin-1 group, and upregulated
protein levels of nephrin and podocin compared to
treatment with siRNA-β-arrestin-1 only.
Conclusions. This study demonstrated that
tripterygium glycoside provided protection against
podocyte injury induced by high-glucose serum, and that
this effect was mediated by the concomitant activation of
autophagy and downregulation of β-arrestin-1.
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