Adiponectin reduces apoptosis of diabetic cardiomyocytes by regulating miR-711/TLR4 axis

Objective: To investigate the regulation of Adiponectin/miR-711 on TLR4/NF-κB-mediated inflammatory response and diabetic cardiomyocyte Apoptosis.

Methods: Diabetes Models were established using rats and H9c2 cardiomyocytes. qRT-PCR was used to detect Adiponectin, miR-711, and TLR4. MTT, β-galactosidase staining, and flow cytometry were utilized to assess cell viability, senescence, and Apoptosis, respectively. The colorimetric method was used to measure Caspase-3 activity, DCFH-DA probes to detect ROS, and western blotting to determine the protein levels of Bax, Bcl-2, TLR4, and p-NF-κB p65. ELISA was performed to measure the levels of Adiponectin, ICAM-1, MCP-1, and IL-1β. Dual-luciferase reporter system examined the targeting relationship between miR-711 and TLR4. H&E and TUNEL staining revealed myocardial structure and Apoptosis, respectively.

Results: Adiponectin and miR-711 were underexpressed and TLR4/NF-κB signaling pathway was activated in high glucose-treated H9c2 cells. High glucose treatment reduced viability, provoked inflammatory response, and accelerated senescence and Apoptosis in H9c2 cells. miR-711 could bind TLR4 mRNA and inactivate TLR4/NF-κB signaling. Adiponectin treatment increased miR-711 expression and blocked TLR4/NF-κB signaling. Adiponectin/miR-711 reduced myocardial inflammation and Apoptosis in diabetic rats.

Conclusion: Adiponectin inhibits inflammation and alleviates high glucose-induced cardiomyocyte Apoptosis by blocking TLR4/NF-κB signaling pathway through miR-711.