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Article

Resveratrol-Elicited PKC Inhibition Counteracts NOX-Mediated Endothelial to Mesenchymal Transition in Human Retinal Endothelial Cells Exposed to High Glucose

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Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE
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Department of Biomedical Sciences, College of Health Sciences Member of QU Health, Qatar University, Doha 2713, Qatar
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Biomedical Research Center, Qatar University, Doha 2713, Qatar
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Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
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Gynecologic and Obstetric Clinic, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
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Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar
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Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha 2713, Qatar
*
Authors to whom correspondence should be addressed.
Academic Editor: Mario Allegra
Antioxidants 2021, 10(2), 224; https://doi.org/10.3390/antiox10020224
Received: 19 November 2020 / Revised: 23 January 2021 / Accepted: 25 January 2021 / Published: 2 February 2021
Diabetes-associated long-term hyperglycaemia leads to oxidative stress-mediated fibrosis in different tissues and organs. Endothelial-to-mesenchymal-transition (EndMT) appears to play a role in diabetes-associated fibrotic conditions. Here, we investigate whether EndMT is implicated in the diabetic retinopathy fibrotic process and evaluate the possibility that resveratrol could counteract EndMT by inhibiting high glucose (HG)-induced increases in ROS. Primary Human Retinal Endothelial Cells (HRECs) were either pre-treated for 24 h with 1 µM resveratrol or left untreated, then glucose (30 mM) was applied at 3-day intervals for 10 days. qRT-PCR and ELISA were used to detect mRNA or protein expression of endothelial markers (CD31, CDH5, vWF) or mesenchymal markers (VIM, αSMA and collagen I), respectively. Intracellular ROS levels were measured with carboxy-DCFDA, while NOX-associated ROS levels were evaluated using the NADPH-specific redox biosensor p47-roGFP. Treatment of HRECs with HG increased intracellular ROS levels and promoted phenotype shifting towards EndMT, evidenced by decreased expression of endothelial markers concomitant with increased expression of mesenchymal ones. HG-induced EndMT appears to be mediated by NADPH-associated ROS generation as pre-treatment of HRECs with resveratrol or the NADPH inhibitor, diphenyleneiodonium chloride (DPI), attenuated ROS production and EndMT transition, suggesting that the effect of resveratrol on HG-induced ROS occurs via down-regulation of NADPH oxidase. It is worth noting that resveratrol or Chelerythrine, a Protein kinase C (PKC) inhibitor, reduce ROS and EndMT in HG-exposed cells, suggesting that NADPH activation occurs via a PKC-dependent mechanism. Taken together, our results provide the basis for a resveratrol-based potential protective therapy to prevent diabetic-associated complications. View Full-Text
Keywords: resveratrol; diabetes; fibrosis; NOX; oxidative stress; EndMT; retinopathy resveratrol; diabetes; fibrosis; NOX; oxidative stress; EndMT; retinopathy
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MDPI and ACS Style

Giordo, R.; Nasrallah, G.K.; Posadino, A.M.; Galimi, F.; Capobianco, G.; Eid, A.H.; Pintus, G. Resveratrol-Elicited PKC Inhibition Counteracts NOX-Mediated Endothelial to Mesenchymal Transition in Human Retinal Endothelial Cells Exposed to High Glucose. Antioxidants 2021, 10, 224. https://doi.org/10.3390/antiox10020224

AMA Style

Giordo R, Nasrallah GK, Posadino AM, Galimi F, Capobianco G, Eid AH, Pintus G. Resveratrol-Elicited PKC Inhibition Counteracts NOX-Mediated Endothelial to Mesenchymal Transition in Human Retinal Endothelial Cells Exposed to High Glucose. Antioxidants. 2021; 10(2):224. https://doi.org/10.3390/antiox10020224

Chicago/Turabian Style

Giordo, Roberta; Nasrallah, Gheyath K.; Posadino, Anna Maria; Galimi, Francesco; Capobianco, Giampiero; Eid, Ali Hussein; Pintus, Gianfranco. 2021. "Resveratrol-Elicited PKC Inhibition Counteracts NOX-Mediated Endothelial to Mesenchymal Transition in Human Retinal Endothelial Cells Exposed to High Glucose" Antioxidants 10, no. 2: 224. https://doi.org/10.3390/antiox10020224

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