Overexpression of PBX1 attenuates oxidative stress and apoptosis in diabetic cardiomyopathy by transcriptionally inhibiting TXNIP.

Diabetic cardiomyopathy (DCM) is a cardiovascular disease specific to patients with diabetes. The pathophysiology of DCM is significantly influenced by oxidative stress and apoptosis, which are critical mechanisms underlying the disease. PBX homeobox 1 (PBX1) is a homeodomain transcription factor, which plays a crucial role in regulating various biological processes. However, the precise molecular mechanism of PBX1 in DCM is still unclear. In this study, we investigated the protective effect of PBX1 against cardiac injury. Male C57BL/6 mice subjected to streptozotocin were used to simulate DCM in vivo. Genetic manipulation of PBX1 mediated by the adeno-associated virus-based vectors was employed to overexpress PBX1 in mice. The findings indicated that PBX1 expression was significantly downregulated in the left ventricular tissues of DCM mice, and overexpression of PBX1 mitigated cardiac fibrosis and enhanced cardiac function. Additionally, our results demonstrated that PBX1 overexpression effectively reduced oxidative stress and apoptosis in DCM-affected mice. To mimic DCM in vitro, human cardiomyocytes AC16 cells were treated with high glucose (HG), and results obtained in vitro were consistent with those in vivo. Mechanistically, PBX1 could bind to the promoter region of thioredoxin interacting protein (TXNIP) and exerted a negative regulatory effect on TXNIP transcription. In conclusion, these results suggest that overexpression of PBX1 attenuates oxidative stress and apoptosis in DCM progression by transcriptionally inhibiting TXNIP expression. PBX1 may be a novel therapeutic candidate for DCM treatment.