circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a
Zhenjun Xu,1,* Kai Zhong,2,* Guanjun Guo,1,* Can Xu,1 Zhizhao Song,1 Dongjin Wang,1 Jun Pan1 1Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of Ch...
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Dove Medical Press
2021
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oai:doaj.org-article:3a4d401eeada4a97b2fc55aeee879e572021-12-02T17:56:50Zcirc_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a1178-7031https://doaj.org/article/3a4d401eeada4a97b2fc55aeee879e572021-11-01T00:00:00Zhttps://www.dovepress.com/circtgfbr2-inhibits-vascular-smooth-muscle-cells-phenotypic-switch-and-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Zhenjun Xu,1,* Kai Zhong,2,* Guanjun Guo,1,* Can Xu,1 Zhizhao Song,1 Dongjin Wang,1 Jun Pan1 1Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Pan; Zhenjun XuDepartment of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of ChinaTel +86 25 68182222-60721Fax +86 25 83105117Email pj791028@163.com; xzj881225@163.comBackground: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in vitro and in vivo.Methods: The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the luciferase reporter plasmid, and the activity was measured using dual-luciferase reporter assay system. And for RNA pulldown, the relative RNA enrichment of circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by β-aminopropionitrile monofumarate (BAPN) was used to verify the role and mechanism of circ_TGFBR2.Results: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers (α-SMA, SM22α) and inhibited the expression of synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression of TGFBR2 suppressed the progression of AD and increased the expression of contractile markers while inhibited the expression of synthetic markers.Conclusion: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.Keywords: aortic dissection, circ_TGFBR2, miR-29a, KLF4, vascular smooth muscle cellsXu ZZhong KGuo GXu CSong ZWang DPan JDove Medical Pressarticleaortic dissectioncirc_tgfbr2mir-29aklf4vascular smooth muscle cellsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5877-5890 (2021) |
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aortic dissection circ_tgfbr2 mir-29a klf4 vascular smooth muscle cells Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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aortic dissection circ_tgfbr2 mir-29a klf4 vascular smooth muscle cells Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Xu Z Zhong K Guo G Xu C Song Z Wang D Pan J circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| description |
Zhenjun Xu,1,* Kai Zhong,2,* Guanjun Guo,1,* Can Xu,1 Zhizhao Song,1 Dongjin Wang,1 Jun Pan1 1Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Pan; Zhenjun XuDepartment of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of ChinaTel +86 25 68182222-60721Fax +86 25 83105117Email pj791028@163.com; xzj881225@163.comBackground: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in vitro and in vivo.Methods: The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the luciferase reporter plasmid, and the activity was measured using dual-luciferase reporter assay system. And for RNA pulldown, the relative RNA enrichment of circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by β-aminopropionitrile monofumarate (BAPN) was used to verify the role and mechanism of circ_TGFBR2.Results: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers (α-SMA, SM22α) and inhibited the expression of synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression of TGFBR2 suppressed the progression of AD and increased the expression of contractile markers while inhibited the expression of synthetic markers.Conclusion: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.Keywords: aortic dissection, circ_TGFBR2, miR-29a, KLF4, vascular smooth muscle cells |
| format |
article |
| author |
Xu Z Zhong K Guo G Xu C Song Z Wang D Pan J |
| author_facet |
Xu Z Zhong K Guo G Xu C Song Z Wang D Pan J |
| author_sort |
Xu Z |
| title |
circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| title_short |
circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| title_full |
circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| title_fullStr |
circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| title_full_unstemmed |
circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a |
| title_sort |
circ_tgfbr2 inhibits vascular smooth muscle cells phenotypic switch and suppresses aortic dissection progression by sponging mir-29a |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/3a4d401eeada4a97b2fc55aeee879e57 |
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