Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans
Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascula...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2017-08-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/480212 |
| _version_ | 1818339881782345728 |
|---|---|
| author | Shui-chuan Huang Mian Wang Wei-bin Wu Rui Wang Jin Cui Wen Li Zi-lun Li Wen Li Shen-ming Wang |
| author_facet | Shui-chuan Huang Mian Wang Wei-bin Wu Rui Wang Jin Cui Wen Li Zi-lun Li Wen Li Shen-ming Wang |
| author_sort | Shui-chuan Huang |
| collection | DOAJ |
| description | Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Methods: Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO. |
| first_indexed | 2024-12-13T15:34:03Z |
| format | Article |
| id | doaj.art-9cfeec690d4741bb8b54f95f8349f7f7 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T15:34:03Z |
| publishDate | 2017-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-9cfeec690d4741bb8b54f95f8349f7f72022-12-21T23:40:06ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-08-014262492250610.1159/000480212480212Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis ObliteransShui-chuan HuangMian WangWei-bin WuRui WangJin CuiWen LiZi-lun LiWen LiShen-ming WangBackground: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Methods: Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO.http://www.karger.com/Article/FullText/480212Mirna-22-3pArteriosclerosisHuman arterial smooth muscle cellProliferationMigrationNeointimal hyperplasiaHMGB1 |
| spellingShingle | Shui-chuan Huang Mian Wang Wei-bin Wu Rui Wang Jin Cui Wen Li Zi-lun Li Wen Li Shen-ming Wang Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans Cellular Physiology and Biochemistry Mirna-22-3p Arteriosclerosis Human arterial smooth muscle cell Proliferation Migration Neointimal hyperplasia HMGB1 |
| title | Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans |
| title_full | Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans |
| title_fullStr | Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans |
| title_full_unstemmed | Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans |
| title_short | Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans |
| title_sort | mir 22 3p inhibits arterial smooth muscle cell proliferation and migration and neointimal hyperplasia by targeting hmgb1 in arteriosclerosis obliterans |
| topic | Mirna-22-3p Arteriosclerosis Human arterial smooth muscle cell Proliferation Migration Neointimal hyperplasia HMGB1 |
| url | http://www.karger.com/Article/FullText/480212 |
| work_keys_str_mv | AT shuichuanhuang mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT mianwang mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT weibinwu mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT ruiwang mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT jincui mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT wenli mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT zilunli mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT wenli mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans AT shenmingwang mir223pinhibitsarterialsmoothmusclecellproliferationandmigrationandneointimalhyperplasiabytargetinghmgb1inarteriosclerosisobliterans |