Regulated Hyaluronan Synthesis by Vascular Cells
Cellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA) content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of H...
| Autors principals: | , , , , , , |
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| Format: | Article |
| Idioma: | English |
| Publicat: |
Hindawi Limited
2015-01-01
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| Col·lecció: | International Journal of Cell Biology |
| Accés en línia: | http://dx.doi.org/10.1155/2015/208303 |
| _version_ | 1827001972581990400 |
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| author | Manuela Viola Evgenia Karousou Maria Luisa D’Angelo Ilaria Caon Giancarlo De Luca Alberto Passi Davide Vigetti |
| author_facet | Manuela Viola Evgenia Karousou Maria Luisa D’Angelo Ilaria Caon Giancarlo De Luca Alberto Passi Davide Vigetti |
| author_sort | Manuela Viola |
| collection | DOAJ |
| description | Cellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA) content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of HA synthase 2 (HAS2) and other covalent modifications including ubiquitination and O-GlcNAcylation. Substrate availability is important in HA synthesis control. Specific drugs reducing the UDP precursors are able to reduce HA synthesis whereas the hexosamine biosynthetic pathway (HBP) increases the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. The flux through the HBP in the regulation of HA biosynthesis in human aortic vascular smooth muscle cells (VSMCs) was reported as a critical aspect. In fact, inhibiting O-GlcNAcylation reduced HA production whereas increased O-GlcNAcylation augmented HA secretion. Additionally, O-GlcNAcylation regulates HAS2 gene expression resulting in accumulation of its mRNA after induction of O-GlcNAcylation with glucosamine treatments. The oxidized LDLs, the most common molecules related to atherosclerosis outcome and progression, are also able to induce a strong HA synthesis when they are in contact with vascular cells. In this review, we present recent described mechanisms involved in HA synthesis regulation and their role in atherosclerosis outcome and development. |
| first_indexed | 2024-04-12T13:02:41Z |
| format | Article |
| id | doaj.art-98cc9744f59d46a9a7d901b1b37fd894 |
| institution | Directory Open Access Journal |
| issn | 1687-8876 1687-8884 |
| language | English |
| last_indexed | 2025-02-18T11:05:55Z |
| publishDate | 2015-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj.art-98cc9744f59d46a9a7d901b1b37fd8942024-11-02T05:23:58ZengHindawi LimitedInternational Journal of Cell Biology1687-88761687-88842015-01-01201510.1155/2015/208303208303Regulated Hyaluronan Synthesis by Vascular CellsManuela Viola0Evgenia Karousou1Maria Luisa D’Angelo2Ilaria Caon3Giancarlo De Luca4Alberto Passi5Davide Vigetti6Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, ItalyCellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA) content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of HA synthase 2 (HAS2) and other covalent modifications including ubiquitination and O-GlcNAcylation. Substrate availability is important in HA synthesis control. Specific drugs reducing the UDP precursors are able to reduce HA synthesis whereas the hexosamine biosynthetic pathway (HBP) increases the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. The flux through the HBP in the regulation of HA biosynthesis in human aortic vascular smooth muscle cells (VSMCs) was reported as a critical aspect. In fact, inhibiting O-GlcNAcylation reduced HA production whereas increased O-GlcNAcylation augmented HA secretion. Additionally, O-GlcNAcylation regulates HAS2 gene expression resulting in accumulation of its mRNA after induction of O-GlcNAcylation with glucosamine treatments. The oxidized LDLs, the most common molecules related to atherosclerosis outcome and progression, are also able to induce a strong HA synthesis when they are in contact with vascular cells. In this review, we present recent described mechanisms involved in HA synthesis regulation and their role in atherosclerosis outcome and development.http://dx.doi.org/10.1155/2015/208303 |
| spellingShingle | Manuela Viola Evgenia Karousou Maria Luisa D’Angelo Ilaria Caon Giancarlo De Luca Alberto Passi Davide Vigetti Regulated Hyaluronan Synthesis by Vascular Cells International Journal of Cell Biology |
| title | Regulated Hyaluronan Synthesis by Vascular Cells |
| title_full | Regulated Hyaluronan Synthesis by Vascular Cells |
| title_fullStr | Regulated Hyaluronan Synthesis by Vascular Cells |
| title_full_unstemmed | Regulated Hyaluronan Synthesis by Vascular Cells |
| title_short | Regulated Hyaluronan Synthesis by Vascular Cells |
| title_sort | regulated hyaluronan synthesis by vascular cells |
| url | http://dx.doi.org/10.1155/2015/208303 |
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