Silencing of heart and neural crest derivatives expressed transcript 2 attenuates transforming growth factor-β1-enhanced apoptosis of human bronchial epithelial cells

Human bronchial epithelial (HBE) cells form the first protective barrier of the airway to protect patients from pulmonary diseases. The present study was performed to illustrate the mechanism underlying the effect of silencing heart and neural crest derivatives expressed transcript 2 (HAND2) on attenuating the transforming growth factor (TGF)-β1-enhanced apoptosis of HBE cells. TGF-β1 (10 µg/ml) was applied to HBE cells, and the HBE cells were transfected with small interfering RNA targeting HAND2 or were transfected with non-specific sequence. Subsequently, cell proliferation was measured using a Cell Counting kit-8 assay, whereas cell cycle and apoptosis status were measured using a flow cytometer. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the expression levels of cell cycle- and apoptosis-related factors. Western blot analysis was also used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK), P38 and c-Jun-N-terminal kinase (JNK) of mitogen-activated protein kinase (MAPK) pathways. The results showed that TGF-β1 decreased HBE cell proliferation ability, arrested cell cycle at the G(2) phase and promoted cell apoptosis with statistical significance. The expression levels of P21 and Cyclin D1 were inhibited, and those of caspase-3, caspase-8 and caspase-9 were promoted by TGF-β1. The phosphorylation levels of ERK, P38 and JNK were increased by TGF-β1. HAND2-silencing significantly alleviated the above functions of TGF-β1 on the HBE cells. In conclusion, the silencing of HAND2 attenuated the TGF-β1-stimulated apoptosis of HBE cells through regulating cell cycle, apoptosis-related factors and ERK/P38/JNK MAPK pathways. This may provide a novel treatment strategy for pulmonary disease, with HAND2 as the novel gene target.