miRNA-92a Inhibits the Phenotypic Modulation of Vascular Smooth Muscle Cells and May Help to Prevent In-Stent Restenosis
Abstract The modulation of the phenotype of vascular smooth muscle cells (VSMCs) during cell proliferation and migration may represent a potential therapeutic approach for the prevention of vascular intimal hyperplasia. However, the precise role of this process in the biology and remodeling of VSMCs remains unclear. Herein, we demonstrate that miR-92a modulates VSMCs to a synthetic phenotype via the KLF4 pathway. Targeting miR-92a in VSMCs with a KLF4 inhibitor suppressed the synthetic phenotype and inhibited the proliferation and migration of VSMCs. To provide definitive evidence, we measured the expression levels of miR-92a in patients undergoing coronary artery intervention; serum miR-92a levels were significantly higher in patients with In-stent restenosis (ISR) than in those without ISR; these findings were the opposite of those obtained for KLF4. Bioinformatics analysis and promoter-luciferase reporter assays were used to examine the regulatory mechanisms underlying KLF4 expression; we found that KLF4 was transcriptionally upregulated by miR-92a in VSMCs. miRNA transfection was also performed to regulate the expression of miR-92a e. We found that the overexpression of miR-92a inhibited the proliferation and migration of VSMCs and also increased differentiated gene and protein expression. Finally, we found that the inhibition of miR-92a promoted the proliferation and migration of VSMCs; this could be reversed by applying a KLF4 inhibitor. Collectively, these results indicate that the local delivery of a KLF4 inhibitor may act as a novel therapeutic option to prevent in-stent restenosis..
| Medienart: |
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 23. März Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jiang, Fenfen [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-1085399/v1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
XRA035413530 |
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| 520 | |a Abstract The modulation of the phenotype of vascular smooth muscle cells (VSMCs) during cell proliferation and migration may represent a potential therapeutic approach for the prevention of vascular intimal hyperplasia. However, the precise role of this process in the biology and remodeling of VSMCs remains unclear. Herein, we demonstrate that miR-92a modulates VSMCs to a synthetic phenotype via the KLF4 pathway. Targeting miR-92a in VSMCs with a KLF4 inhibitor suppressed the synthetic phenotype and inhibited the proliferation and migration of VSMCs. To provide definitive evidence, we measured the expression levels of miR-92a in patients undergoing coronary artery intervention; serum miR-92a levels were significantly higher in patients with In-stent restenosis (ISR) than in those without ISR; these findings were the opposite of those obtained for KLF4. Bioinformatics analysis and promoter-luciferase reporter assays were used to examine the regulatory mechanisms underlying KLF4 expression; we found that KLF4 was transcriptionally upregulated by miR-92a in VSMCs. miRNA transfection was also performed to regulate the expression of miR-92a e. We found that the overexpression of miR-92a inhibited the proliferation and migration of VSMCs and also increased differentiated gene and protein expression. Finally, we found that the inhibition of miR-92a promoted the proliferation and migration of VSMCs; this could be reversed by applying a KLF4 inhibitor. Collectively, these results indicate that the local delivery of a KLF4 inhibitor may act as a novel therapeutic option to prevent in-stent restenosis. | ||
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