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Article: Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition
Title | Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition |
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Authors | |
Keywords | diabetic nephropathy glomerular endothelial cells microRNA-590-3p phosphofructokinase/fructose bisphosphatase 3 sphingosine 1-phosphate receptor 1 |
Issue Date | 1-Nov-2023 |
Publisher | American Physiological Society |
Citation | American Journal of Physiology: Cell Physiology, 2023, v. 325, n. 5, p. C1354-C1368 How to Cite? |
Abstract | Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment. |
Persistent Identifier | http://hdl.handle.net/10722/339266 |
ISSN | 2023 Impact Factor: 5.0 2023 SCImago Journal Rankings: 1.711 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yu, B | - |
dc.contributor.author | Shen, K | - |
dc.contributor.author | Li, T | - |
dc.contributor.author | Li, J | - |
dc.contributor.author | Meng, M | - |
dc.contributor.author | Liu, W | - |
dc.contributor.author | Tang, Q | - |
dc.contributor.author | Zhu, T | - |
dc.contributor.author | Wang, X | - |
dc.contributor.author | Leung, SWS | - |
dc.contributor.author | Shi, Y. | - |
dc.date.accessioned | 2024-03-11T10:35:16Z | - |
dc.date.available | 2024-03-11T10:35:16Z | - |
dc.date.issued | 2023-11-01 | - |
dc.identifier.citation | American Journal of Physiology: Cell Physiology, 2023, v. 325, n. 5, p. C1354-C1368 | - |
dc.identifier.issn | 0363-6143 | - |
dc.identifier.uri | http://hdl.handle.net/10722/339266 | - |
dc.description.abstract | <p>Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.</p> | - |
dc.language | eng | - |
dc.publisher | American Physiological Society | - |
dc.relation.ispartof | American Journal of Physiology: Cell Physiology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | diabetic nephropathy | - |
dc.subject | glomerular endothelial cells | - |
dc.subject | microRNA-590-3p | - |
dc.subject | phosphofructokinase/fructose bisphosphatase 3 | - |
dc.subject | sphingosine 1-phosphate receptor 1 | - |
dc.title | Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition | - |
dc.type | Article | - |
dc.identifier.doi | 10.1152/ajpcell.00261.2023 | - |
dc.identifier.scopus | eid_2-s2.0-85176460564 | - |
dc.identifier.volume | 325 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | C1354 | - |
dc.identifier.epage | C1368 | - |
dc.identifier.eissn | 1522-1563 | - |
dc.identifier.isi | WOS:001143763800001 | - |
dc.identifier.issnl | 0363-6143 | - |