Podocyte apoptosis and
mitochondrial dysfunction serve a major role in
diabetic nephropathy progression. The present study revealed a molecular mechanism regulating podocyte apoptosis and
mitochondrial dysfunction. In vitro models were established using conditionally immortalized mouse podocyte clonal cells treated with high
glucose (HG). Reverse quantitative-transcription PCR were used to detect gene expression, western blotting and immunofluorescence were used to detect
protein expression, Cell Counting Kit-8 was used to detect cell viability and flow cytometry was used to detect cell apoptosis. HG treatment in the mouse podocyte clonal cells downregulated
taurine-upregulated gene 1 (TUG1) expression and decreased viability in a dose-dependent manner. In addition, TUG1 knockdown (KD) increased HG-induced apoptosis, while TUG1 overexpression (OE) reduced HG-induced apoptosis in podocytes. HG-induced
mitochondrial dysfunction was identified in podocytes, with increased
reactive oxygen species levels, decreased complex I/III activity and decreased basal/maximal oxygen consumption rate. TUG1 KD worsened HG-induced
mitochondrial dysfunction, and TUG1 OE reversed these effects. At the molecular level, TUG1 was revealed to promote
sirtuin 1 (
SIRT1) expression by sponging
microRNA (miR)-9, and
SIRT1 OE reversed the HG-induced apoptosis and
mitochondrial dysfunction increased by TUG1 KD. The present data indicated that downregulation of TUG1 induced by HG was associated with HG-induced apoptosis and
mitochondrial dysfunction in podocytes, and that TUG1 protected HG-induced podocytes by promoting
SIRT1 expression via miR-9 inhibition.