Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes
Diabetes-induced endothelial pathologies are hypothesized to lead to the progression of diabetic kidney disease (DKD). The endothelial to mesenchymal transition (EndMT) possibly induces fibrosis, leading to glomerulosclerosis in the kidney. Furthermore, this could lead to albuminuria in diabetic nep...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2021/2182225 |
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| author | Toshinori Yasuzawa Tomomi Nakamura Shigeru Ueshima Akira Mima |
| author_facet | Toshinori Yasuzawa Tomomi Nakamura Shigeru Ueshima Akira Mima |
| author_sort | Toshinori Yasuzawa |
| collection | DOAJ |
| description | Diabetes-induced endothelial pathologies are hypothesized to lead to the progression of diabetic kidney disease (DKD). The endothelial to mesenchymal transition (EndMT) possibly induces fibrosis, leading to glomerulosclerosis in the kidney. Furthermore, this could lead to albuminuria in diabetic nephropathy due to glomerular endothelial dysfunction. Eicosapentaenoic acid (EPA), purified from fish oil, decreases inflammatory cytokine levels in glomerulonephritis. Here, we aimed at finding whether ethyl eicosapentaenoate (EPA-E) exerts renal protective effects via EndMT inhibition. To find out whether EPA inhibits EndMT in vitro, the changes in CD31 expression were studied in cultured mouse endothelial cells. The addition of the conditioned medium from the adipocyte culture significantly decreased the protein levels of CD31, while the addition of EPA-E partially reversed this inhibition. Further, EndMT inhibition by EPA-E treatment might occur via the inhibition of the protein kinase Cβ (PKCβ)/transforming growth factor-β (TGF-β)/plasminogen activator inhibitor-1 (PAI-1) signaling and not via microRNAs. Streptozotocin-induced diabetic mice fed a high-fat diet (60% from fat) exhibited mesangial expansion and albuminuria. Induction of EPA-E ameliorated the mesangial expansion and decreased albuminuria without affecting blood pressure, triglyceride and free fatty acid levels, and intraperitoneal glucose. These findings suggest that EPA-E exerts renal protective effects on endothelial cells, by normalizing EndMT followed by the PKCβ/TGF-β/PAI-1 signaling. Thus, EPA-E has the potential for imparting renal protection by regulating EndMT in DKD. |
| format | Article |
| id | doaj-art-6bd88a275bd549fba1b24958fe56ca9a |
| institution | OA Journals |
| issn | 2314-6753 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-6bd88a275bd549fba1b24958fe56ca9a2025-08-20T02:06:11ZengWileyJournal of Diabetes Research2314-67532021-01-01202110.1155/2021/2182225Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in DiabetesToshinori Yasuzawa0Tomomi Nakamura1Shigeru Ueshima2Akira Mima3Department of NephrologyDepartment of Food Science and NutritionDepartment of Food Science and NutritionDepartment of NephrologyDiabetes-induced endothelial pathologies are hypothesized to lead to the progression of diabetic kidney disease (DKD). The endothelial to mesenchymal transition (EndMT) possibly induces fibrosis, leading to glomerulosclerosis in the kidney. Furthermore, this could lead to albuminuria in diabetic nephropathy due to glomerular endothelial dysfunction. Eicosapentaenoic acid (EPA), purified from fish oil, decreases inflammatory cytokine levels in glomerulonephritis. Here, we aimed at finding whether ethyl eicosapentaenoate (EPA-E) exerts renal protective effects via EndMT inhibition. To find out whether EPA inhibits EndMT in vitro, the changes in CD31 expression were studied in cultured mouse endothelial cells. The addition of the conditioned medium from the adipocyte culture significantly decreased the protein levels of CD31, while the addition of EPA-E partially reversed this inhibition. Further, EndMT inhibition by EPA-E treatment might occur via the inhibition of the protein kinase Cβ (PKCβ)/transforming growth factor-β (TGF-β)/plasminogen activator inhibitor-1 (PAI-1) signaling and not via microRNAs. Streptozotocin-induced diabetic mice fed a high-fat diet (60% from fat) exhibited mesangial expansion and albuminuria. Induction of EPA-E ameliorated the mesangial expansion and decreased albuminuria without affecting blood pressure, triglyceride and free fatty acid levels, and intraperitoneal glucose. These findings suggest that EPA-E exerts renal protective effects on endothelial cells, by normalizing EndMT followed by the PKCβ/TGF-β/PAI-1 signaling. Thus, EPA-E has the potential for imparting renal protection by regulating EndMT in DKD.http://dx.doi.org/10.1155/2021/2182225 |
| spellingShingle | Toshinori Yasuzawa Tomomi Nakamura Shigeru Ueshima Akira Mima Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes Journal of Diabetes Research |
| title | Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes |
| title_full | Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes |
| title_fullStr | Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes |
| title_full_unstemmed | Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes |
| title_short | Protective Effects of Eicosapentaenoic Acid on the Glomerular Endothelium via Inhibition of EndMT in Diabetes |
| title_sort | protective effects of eicosapentaenoic acid on the glomerular endothelium via inhibition of endmt in diabetes |
| url | http://dx.doi.org/10.1155/2021/2182225 |
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