Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis
Abstract Tanshinone IIA (Tan IIA) has an important role in treatment of cardiovascular diseases, including atherosclerosis. The vascular smooth muscle cells (VSMCs) are a major part of the atherosclerotic plaque. However, the biological functions of Tan IIA in regulating VSMCs function remain mostly...
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12663 |
| _version_ | 1827930888883666944 |
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| author | Wei Li Zhi Gao Qing‐Long Guan |
| author_facet | Wei Li Zhi Gao Qing‐Long Guan |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Abstract Tanshinone IIA (Tan IIA) has an important role in treatment of cardiovascular diseases, including atherosclerosis. The vascular smooth muscle cells (VSMCs) are a major part of the atherosclerotic plaque. However, the biological functions of Tan IIA in regulating VSMCs function remain mostly unclear. This research aimed at identifying the explicit molecular mechanism that Tan IIA regulates oxidized low‐density lipoprotein (ox‐LDL)‐mediated VSMC proliferation and migration. VSMCs challenged by ox‐LDL were adopted as cellular model of atherosclerosis, and suffered from Tan IIA treatment. After that, cells proliferation, apoptosis or migration were measured. The expression levels of microRNA (miR)‐137, transient receptor potential cation channel subfamily C member 3 (TRPC3) and proliferating cell nuclear antigen (PCNA) were measured. The targeting relationship between miR‐137 and TRPC3 was determined. It was found that Tan IIA blunted VSMC proliferation, PCNA expression and migration mediated by ox‐LDL. Tan IIA promoted miR‐137 level, and miR‐137 knockdown reversed the influences of Tan IIA on VSMC proliferation, PCNA expression and migration in the presence of ox‐LDL. TRPC3 was verified to be targeted by miR‐137. Moreover, TRPC3 silencing exacerbated the influences of Tan IIA on VSMC proliferation, apoptosis and migration, and it mitigated the inhibitive effects of miR‐137 knockdown on function of Tan IIA. We confirmed for the first time that Tan IIA constrained ox‐LDL‐stimulated VSMC proliferation and migration via regulating the miR‐137/TRPC3 axis, which provided a theoretical basis for the research and promotion of Tan IIA as a therapeutic drug. |
| first_indexed | 2024-03-13T06:43:47Z |
| format | Article |
| id | doaj.art-e6552918832c45dba3ee667040647814 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-03-13T06:43:47Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-e6552918832c45dba3ee6670406478142023-06-08T13:32:18ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-06-0139659660410.1002/kjm2.12663Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axisWei Li0Zhi Gao1Qing‐Long Guan2Department of Vascular Surgery The Second Hospital of Yinzhou District Ningbo Zhejiang Province People's Republic of ChinaDepartment of Orthopedic Surgery The Second Hospital of Yinzhou District Ningbo Zhejiang Province People's Republic of ChinaDepartment of Vascular Surgery The Second Affiliated Hospital of Shandong First Medical University Taian Shandong Province People's Republic of ChinaAbstract Tanshinone IIA (Tan IIA) has an important role in treatment of cardiovascular diseases, including atherosclerosis. The vascular smooth muscle cells (VSMCs) are a major part of the atherosclerotic plaque. However, the biological functions of Tan IIA in regulating VSMCs function remain mostly unclear. This research aimed at identifying the explicit molecular mechanism that Tan IIA regulates oxidized low‐density lipoprotein (ox‐LDL)‐mediated VSMC proliferation and migration. VSMCs challenged by ox‐LDL were adopted as cellular model of atherosclerosis, and suffered from Tan IIA treatment. After that, cells proliferation, apoptosis or migration were measured. The expression levels of microRNA (miR)‐137, transient receptor potential cation channel subfamily C member 3 (TRPC3) and proliferating cell nuclear antigen (PCNA) were measured. The targeting relationship between miR‐137 and TRPC3 was determined. It was found that Tan IIA blunted VSMC proliferation, PCNA expression and migration mediated by ox‐LDL. Tan IIA promoted miR‐137 level, and miR‐137 knockdown reversed the influences of Tan IIA on VSMC proliferation, PCNA expression and migration in the presence of ox‐LDL. TRPC3 was verified to be targeted by miR‐137. Moreover, TRPC3 silencing exacerbated the influences of Tan IIA on VSMC proliferation, apoptosis and migration, and it mitigated the inhibitive effects of miR‐137 knockdown on function of Tan IIA. We confirmed for the first time that Tan IIA constrained ox‐LDL‐stimulated VSMC proliferation and migration via regulating the miR‐137/TRPC3 axis, which provided a theoretical basis for the research and promotion of Tan IIA as a therapeutic drug.https://doi.org/10.1002/kjm2.12663atherosclerosismiR‐137ox‐LDLTanshinone IIATRPC3 |
| spellingShingle | Wei Li Zhi Gao Qing‐Long Guan Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis Kaohsiung Journal of Medical Sciences atherosclerosis miR‐137 ox‐LDL Tanshinone IIA TRPC3 |
| title | Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis |
| title_full | Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis |
| title_fullStr | Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis |
| title_full_unstemmed | Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis |
| title_short | Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis |
| title_sort | tan iia mitigates vascular smooth muscle cell proliferation and migration induced by ox ldl through the mir 137 trpc3 axis |
| topic | atherosclerosis miR‐137 ox‐LDL Tanshinone IIA TRPC3 |
| url | https://doi.org/10.1002/kjm2.12663 |
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