Deregulation of long noncoding RNA (TUG1) contributes to excessive podocytes apoptosis by activating endoplasmic reticulum stress in the development of diabetic nephropathy

The objective of this study was to investigate the molecular mechanism of how TUG1 interferes with the expression of C/EBP homologous protein (CHOP), peroxisome-proliferator-activated receptor- coactivator-1 alpha (PGC-1), which contributes to the development of diabetic nephropathy. Real-time polymerase chain reaction and western blot analysis were performed to explore the regulatory relationship among TUG1, CHOP, PGC-1, and caspase-3. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was performed to confirm TUG1 involved in diabetic nephropathy (DN) through influencing podocytes apoptosis. TUG1 was highly expressed in a cell following treatment with high glucose, and PGC-1 and cleaved caspase-3 levels were much lower, while CHOP level was much higher in high glucose group (HG), furthermore, CHOP inhibited PGC-1 expression. TUG1 negatively regulated CHOP expression, and positively regulated PGC-1 expression. Meanwhile, total caspase-3 level in cell treated with or without HG transfected with CHOP small interfering ribonucleic acid (siRNA), TUG1, and TUG1 siRNA showed no evident difference with their corresponding control, while CHOP siRNA and TUG1 evidently decreased, and TUG1 siRNA remarkably increased cleaved caspase-3 level in HG or normal glucose groups in comparison with corresponding control. TUG1 and PGC-1 levels were much lower, while CHOP level was much higher in participants diagnosed with DN. A higher level of CHOP protein and lower level of PGC-1 were observed in subjects diagnosed with DN. Finally, podocytes apoptosis in the DN group was significantly promoted compared with that in nondiabetic renal disease group. Our current study has suggested for the first time that the long noncoding RNA (lncRNA) TUG1 influenced podocytes apoptosis via mediating endoplasmic reticulum stress (ERS)-CHOP-PGC-1 signaling pathway in HG-induced DN.