Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis
Abstract Objective This study aimed to determine the effects of emodin on the viability, proliferation and apoptosis of human pulmonary artery smooth muscle cells (PASMCs) under hypoxia and to explore the underling molecular mechanisms. Methods PASMCs were cultured in a hypoxic environment (1% oxyge...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-021-01616-1 |
| _version_ | 1818655612132655104 |
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| author | Li Yi JunFang Liu Ming Deng Huihua Zuo Mingyan Li |
| author_facet | Li Yi JunFang Liu Ming Deng Huihua Zuo Mingyan Li |
| author_sort | Li Yi |
| collection | DOAJ |
| description | Abstract Objective This study aimed to determine the effects of emodin on the viability, proliferation and apoptosis of human pulmonary artery smooth muscle cells (PASMCs) under hypoxia and to explore the underling molecular mechanisms. Methods PASMCs were cultured in a hypoxic environment (1% oxygen) and then treated with emodin. Cell viability, proliferation and apoptosis were evaluated using CCK-8 assay, EdU staining assay, western blot and Mito-tracker red CMXRos and Annexin V-FITC apoptosis detection assay. The microRNA (miRNA)/mRNA and protein expression levels were assessed by quantitative real-time PCR and western blotting, respectively. Based on transcriptomics and proteomics were used to identify potential signaling pathways. Luciferase reporter assay was utilized to examine the interaction between miR-244-5p and DEGS1. Results Emodin at 40 and 160 µM concentration-dependently suppressed cell viability, proliferation and migration, but enhanced cell apoptosis of PASMCs under hypoxia. Transcriptomic and proteomic analysis revealed that emodin could attenuate the activity of PI3K/Akt signaling in PASMCs under hypoxia. In addition, delta 4-desaturase, sphingolipid 1 (DEGS1) was found to be a direct target of miR-244-5p. Emodin could significantly up-regulated miR-244-5p expression and down-regulated DEGS1 expression in PASMCs under hypoxia. Furthermore, emodin-mediated effects on cell viability, migration, apoptosis and PI3K/Akt signaling activity of PASMCs under hypoxia were significantly attenuated by miR-244-5p knockdown. Conclusions Our results indicated that emodin suppressed cell viability, proliferation and migration, promoted cell apoptosis of PASMCs under hypoxia via modulating miR-244-5p-mediated DEGS1/PI3K/Akt signaling pathway. MiR-244-5p/DEGS1 axis was initially investigated in this current study, which is expected to further the understanding of the etiology of pulmonary arterial hypertension. |
| first_indexed | 2024-12-17T03:12:27Z |
| format | Article |
| id | doaj.art-fbae7e3a85bc4e1cb3a13acde3b0cd47 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-12-17T03:12:27Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-fbae7e3a85bc4e1cb3a13acde3b0cd472022-12-21T22:05:48ZengBMCBMC Pulmonary Medicine1471-24662021-07-0121111610.1186/s12890-021-01616-1Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axisLi Yi0JunFang Liu1Ming Deng2Huihua Zuo3Mingyan Li4Special Medical Service Center, Zhujiang Hospital, Southern Medical UniversityPulmonary and Critical Care Medicine, Zhujiang Hospital of Southern Medical UniversityDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical SciencesDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical SciencesDepartment of Cardiology, The Second Affiliated Hospital of Guangzhou Medical UniversityAbstract Objective This study aimed to determine the effects of emodin on the viability, proliferation and apoptosis of human pulmonary artery smooth muscle cells (PASMCs) under hypoxia and to explore the underling molecular mechanisms. Methods PASMCs were cultured in a hypoxic environment (1% oxygen) and then treated with emodin. Cell viability, proliferation and apoptosis were evaluated using CCK-8 assay, EdU staining assay, western blot and Mito-tracker red CMXRos and Annexin V-FITC apoptosis detection assay. The microRNA (miRNA)/mRNA and protein expression levels were assessed by quantitative real-time PCR and western blotting, respectively. Based on transcriptomics and proteomics were used to identify potential signaling pathways. Luciferase reporter assay was utilized to examine the interaction between miR-244-5p and DEGS1. Results Emodin at 40 and 160 µM concentration-dependently suppressed cell viability, proliferation and migration, but enhanced cell apoptosis of PASMCs under hypoxia. Transcriptomic and proteomic analysis revealed that emodin could attenuate the activity of PI3K/Akt signaling in PASMCs under hypoxia. In addition, delta 4-desaturase, sphingolipid 1 (DEGS1) was found to be a direct target of miR-244-5p. Emodin could significantly up-regulated miR-244-5p expression and down-regulated DEGS1 expression in PASMCs under hypoxia. Furthermore, emodin-mediated effects on cell viability, migration, apoptosis and PI3K/Akt signaling activity of PASMCs under hypoxia were significantly attenuated by miR-244-5p knockdown. Conclusions Our results indicated that emodin suppressed cell viability, proliferation and migration, promoted cell apoptosis of PASMCs under hypoxia via modulating miR-244-5p-mediated DEGS1/PI3K/Akt signaling pathway. MiR-244-5p/DEGS1 axis was initially investigated in this current study, which is expected to further the understanding of the etiology of pulmonary arterial hypertension.https://doi.org/10.1186/s12890-021-01616-1EmodinPulmonary arterial hypertensionPulmonary artery smooth muscle cellsProliferationApoptosismiR-244-5p |
| spellingShingle | Li Yi JunFang Liu Ming Deng Huihua Zuo Mingyan Li Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis BMC Pulmonary Medicine Emodin Pulmonary arterial hypertension Pulmonary artery smooth muscle cells Proliferation Apoptosis miR-244-5p |
| title | Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis |
| title_full | Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis |
| title_fullStr | Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis |
| title_full_unstemmed | Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis |
| title_short | Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis |
| title_sort | emodin inhibits viability proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting mir 244 5p degs1 axis |
| topic | Emodin Pulmonary arterial hypertension Pulmonary artery smooth muscle cells Proliferation Apoptosis miR-244-5p |
| url | https://doi.org/10.1186/s12890-021-01616-1 |
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