Background
Diabetic retinopathy (DR) is a microvascular complication associated with damage to the retina due to inflammation induced by high glucose. Activation of the NLRP3 inflammasome plays a critical role in DR and its prevention is beneficial to patients. However, the regulation of long non-coding RNA (lncRNA) in NLRP3 inflammasome activation of DR is incompletely understood. So, this study aimed to uncover the functional and regulatory mechanism of the lncRNA HOTAIR in NLRP3 inflammasome activation in Dr.
Conclusion
The lncRNA HOTAIR promotes NLRP3 inflammasome activation and ROS generation by inhibiting Nrf2 in Dr.
Methods
The vitreous humor was collected from the patients and detected the inflammatory and oxidative stress makers. Human retinal endothelial cells (HRECs) were cultured and stimulated in low D-glucose (5 mmol/L) or high D-glucose (20 mmol/L). Additionally, HRECs were knocked down HOTAIR with a si-RNA. Then, the NLRP3 inflammasome activation was analyzed by western blotting and pyroptosis cell imaging. The ROS was measured by specific probe. The activation of Nrf2 measured by Immunofluorescent staining. The interaction between HOTAIR and Nrf2 was evaluated by co-immunoprecipitation and RNA immunoprecipitation.
Results
The expression of HOTAIR was significantly increased in the vitreous of patients with DR and in HRECs stimulated with high glucose. Furthermore, HOTAIR knockdown relieved NLRP3 inflammasome activation. More specifically, HOTAIR knockdown suppressed the expression of NLRP3, pro-caspase-1, and pro-IL-1β, as well as IL-1β maturation and pyroptosis. HOTAIR knockdown also interfered with the ROS generation induced by high glucose. Moreover, HOTAIR promoted the interaction between Nrf2 and Keap1 by binding and inactivating Nrf2.