Profilin-1 mediates microvascular endothelial dysfunction in diabetic retinopathy through HIF-1α-dependent pathway

Diabetic retinopathy (DR), a well-known serious complication of diabetes mellitus, can eventually advance to end-stage blindness.

To investigate the role of profilin-1 (PFN1) in microvascular endothelial dysfunction (MVED) triggered by DR.

We assessed the expression of PFN1 and hypoxia inducible factor-1 alpha (HIF-1α) in cultured human retinal microvascular endothelial cells (HRMECs) treated with high glucose and in 6 month-old Sprague-Dawley (SD) rats with DR. We also investigated the function of metformin in PFN1-mediated MVED.

High glucose upregulated PFN1 and HIF-1α expression levels. These changes were associated with increased permeability, apoptosis, and angiogenesis in vivo and in vitro. Metformin prevented high glucose or hyperglycemia-induced MVED by inhibition of HIF-1α/PFN1 signaling in cultured HRMECs and in SD rats with DR.

Our results indicate that activation of HIF-1α/PFN1 by high glucose mediates permeability, apoptosis, and angiogenesis and that metformin alleviates MVED by suppressing HIF-1α/PFN1 signaling during DR. These results suggest a potential therapeutic strategy for preventing the onset of PFN1 in early-stage of DR.