High glucose-activated NFAT promotes podocyte apoptosis by down-regulation of PGC-1 / 中国病理生理杂志

ABSTRACT

AIM:To explore whether down-regulation of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α induces podocyte apoptosis and its mechanism.METHODS:The podocytes were cultured under high glucose (HG) condition and the cell apoptosis was analyzed by flow cytometry.The methods of real-time PCR and Western blot were used to analyze the mRNA and protein expression of related molecules in the control, HG-treated or siRNA-treated podocytes.RESULTS:The expression PGC-1α at mRNA and protein levels was significantly decreased in HG-injured podocytes.Down-regulation of PGC-1α expression in vitro by siRNA resulted in podocyte apoptosis.The nuclear protein expression of nuclear factor of activated T-cells (NFAT) was significantly increased in HG injured podocytes, indicating the NFAT activation.Down-regulation of PGC-1α expression also decreased the nuclear protein expression of NFAT.Moreover, silencing of NFAT expression by siRNA significantly abolished PGC-1α deficiency-induced podocyte apoptosis.CONCLUSION: Down-regulation of PGC-1α induces podocyte apoptosis.NFAT mediates PGC-1α deficiency-induced podocyte apoptosis.