Hao Ding1,2, Bin Chen3, Qianyi Lu4, Jian Wang1. 1. Department of General Surgery, Children's Hospital Affiliated to Soochow University Suzhou, China. 2. Department of Clinical Nutrition, Anhui Provincial Children's Hospital Hefei, China. 3. Department of Ophthalmology, Changshu No. 1 People's Hospital Changshu, China. 4. Department of Ophthalmology, The First Affiliated Hospital of Soochow University Suzhou, China.
Abstract
BACKGROUND: Diabetic retinopathy (DR), a well-known serious complication of diabetes mellitus, can eventually advance to end-stage blindness. AIM: To investigate the role of profilin-1 (PFN1) in microvascular endothelial dysfunction (MVED) triggered by DR. METHODS: 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. RESULTS: 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. CONCLUSION: 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. IJCEP
BACKGROUND:Diabetic retinopathy (DR), a well-known serious complication of diabetes mellitus, can eventually advance to end-stage blindness. AIM: To investigate the role of profilin-1 (PFN1) in microvascular endothelial dysfunction (MVED) triggered by DR. METHODS: 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. RESULTS: 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. CONCLUSION: 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. IJCEP
Authors: Abigail Allen; David Gau; Paul Francoeur; Jordan Sturm; Yue Wang; Ryan Martin; Jodi Maranchie; Anette Duensing; Adam Kaczorowski; Stefan Duensing; Lily Wu; Michael T Lotze; David Koes; Walter J Storkus; Partha Roy Journal: J Biol Chem Date: 2020-09-03 Impact factor: 5.157