Dataset Information

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

ABSTRACT: Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe ^-/- mice through the integrin αVβ5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, β-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVβ5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

SUBMITTER: Chen J

PROVIDER: S-EPMC9023791 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Chen Junye J Li Kang K Shao Jiang J Lai Zhichao Z Gao Ran R Wang Chaonan C Song Xitao X Guo Wenjun W Yu Xiaoxi X Du Fenghe F Zhu Zhan Z Wang Jiaxian J Ma Jiangyu J Xu Leyin L Zhou Yan Y Liu Jianghao J Shu Keqiang K Zhao Hongmei H Wang Jing J Liu Bao B

Frontiers in cardiovascular medicine 20220408

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in <i>Apoe</i> <sup>-/-</sup> mi ...[more]

PMID: 35463776

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Project description:BackgroundHepatocellular carcinoma (HCC) has an increasing incidence and high mortality. Surgical operation is not a comprehensive strategy for liver cancer. Moreover, tolerating systemic chemotherapy is difficult for patients with HCC because hepatic function is often impaired due to underlying cirrhosis. Therefore, a comprehensive strategy for cancer treatment should be developed. DTL (Cdc10-dependent transcript 2) is a critical regulator of cell cycle progression and genomic stability. In our previous study, the upregulation of DTL expression in aggressive HCC correlated positively with tumor grade and poor patient survival. We hypothesize that targeting DTL may provide a novel therapeutic strategy for liver cancer. DTL small interference RNAs were used to knock down DTL protein expression.MethodsA clonogenic assay, immunostaining, double thymidine block, imaging flow cytometry analysis, and a tumor spheroid formation assay were used to analyze the role of DTL in tumor cell growth, cell cycle progression, micronucleation, ploidy, and tumorigenicity.ResultsOur results demonstrated that targeting DTL reduced cell cycle regulators and chromosome segregation genes, resulting in increased cell micronucleation. DTL depletion inhibited liver cancer cell growth, increased senescence, and reduced tumorigenesis. DTL depletion resulted in the disruption of the mitotic proteins cyclin B, CDK1, securin, seprase, Aurora A, and Aurora B as well as the upregulation of the cell cycle arrest gene p21. A rescue assay indicated that DTL should be targeted through TPX2 downregulation for cancer cell growth inhibition. Moreover, DTL silencing inhibited the growth of patient-derived primary cultured HCC cells.ConclusionOur study results indicate that DTL is a potential novel target gene for treating liver cancer through liver cancer cell senescence induction. Furthermore, our results provide insights into molecular mechanisms for targeting DTL in liver cancer cells. The results also indicate several other starting points for future preclinical and clinical studies on liver cancer treatment.

Dataset Information

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Publications

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Similar Datasets

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