Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
This study aimed to explore the effects of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells w...
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-02-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2022-0554 |
| _version_ | 1827969135130181632 |
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| author | Shu Jin Shi Jue Gu Yiwen Deng Lei Zhao Chen Wu Chun Zhao Jiachen Wang Haiya Jin Li |
| author_facet | Shu Jin Shi Jue Gu Yiwen Deng Lei Zhao Chen Wu Chun Zhao Jiachen Wang Haiya Jin Li |
| author_sort | Shu Jin |
| collection | DOAJ |
| description | This study aimed to explore the effects of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP‐1-OE plasmid/si‑TIMP‐1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated Axl, α-SMA, and MMP3 expression (P < 0.05) and downregulated STAT4 and TIMP1 expression (P < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis (P < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated Axl, AT1R, α-SMA, collagen III, Bcl-2, and MMP3 expression caused by AngII and upregulated caspase 3, p53, and STAT4 expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression. |
| first_indexed | 2024-04-09T18:33:17Z |
| format | Article |
| id | doaj.art-ab943acf3af349b2b0f417e28d177b78 |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-04-09T18:33:17Z |
| publishDate | 2023-02-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj.art-ab943acf3af349b2b0f417e28d177b782023-04-11T17:07:13ZengDe GruyterOpen Life Sciences2391-54122023-02-0118132728710.1515/biol-2022-0554Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1Shu Jin0Shi Jue1Gu Yiwen2Deng Lei3Zhao Chen4Wu Chun5Zhao Jiachen6Wang Haiya7Jin Li8Department of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaDepartment of Gerontology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200023, ChinaDepartment of Gerontology, Shibei Hospital of Jing’an District, Shanghai, 200443, ChinaThis study aimed to explore the effects of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP‐1-OE plasmid/si‑TIMP‐1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated Axl, α-SMA, and MMP3 expression (P < 0.05) and downregulated STAT4 and TIMP1 expression (P < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis (P < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated Axl, AT1R, α-SMA, collagen III, Bcl-2, and MMP3 expression caused by AngII and upregulated caspase 3, p53, and STAT4 expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression.https://doi.org/10.1515/biol-2022-0554tissue inhibitor of metalloproteinases-1myocardial fibrosislevocarnitineangiotensin ii |
| spellingShingle | Shu Jin Shi Jue Gu Yiwen Deng Lei Zhao Chen Wu Chun Zhao Jiachen Wang Haiya Jin Li Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 Open Life Sciences tissue inhibitor of metalloproteinases-1 myocardial fibrosis levocarnitine angiotensin ii |
| title | Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 |
| title_full | Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 |
| title_fullStr | Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 |
| title_full_unstemmed | Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 |
| title_short | Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1 |
| title_sort | levocarnitine regulates the growth of angiotensin ii induced myocardial fibrosis cells via timp 1 |
| topic | tissue inhibitor of metalloproteinases-1 myocardial fibrosis levocarnitine angiotensin ii |
| url | https://doi.org/10.1515/biol-2022-0554 |
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