MKI67 as a potential diagnostic biomarker in pulmonary hypertension
BackgroundRight heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fi...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2022-11-01
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Series: | Frontiers in Pediatrics |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.1016889/full |
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author | Huiling Zhou Ke Gong Yifeng Yang Qin Wu Qiuguo Wang Yadan Shen Yadan Shen Li Xie Yibo Gong Haidan Liu Haidan Liu Jijia Liu |
author_facet | Huiling Zhou Ke Gong Yifeng Yang Qin Wu Qiuguo Wang Yadan Shen Yadan Shen Li Xie Yibo Gong Haidan Liu Haidan Liu Jijia Liu |
author_sort | Huiling Zhou |
collection | DOAJ |
description | BackgroundRight heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets.MethodsMonocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs.ResultsAfter sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased.ConclusionSeveral potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67. |
first_indexed | 2024-04-11T08:21:03Z |
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institution | Directory Open Access Journal |
issn | 2296-2360 |
language | English |
last_indexed | 2024-04-11T08:21:03Z |
publishDate | 2022-11-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Pediatrics |
spelling | doaj.art-1bde695a061f4550af8997b6d3288bc52022-12-22T04:34:57ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-11-011010.3389/fped.2022.10168891016889MKI67 as a potential diagnostic biomarker in pulmonary hypertensionHuiling Zhou0Ke Gong1Yifeng Yang2Qin Wu3Qiuguo Wang4Yadan Shen5Yadan Shen6Li Xie7Yibo Gong8Haidan Liu9Haidan Liu10Jijia Liu11Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaExtracorporeal Life Support Center of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaThe Clinical Center for Gene Diagnosis and Therapy of the State Key Laboratory of Medical Genetics, the Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, ChinaBackgroundRight heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets.MethodsMonocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs.ResultsAfter sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased.ConclusionSeveral potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67.https://www.frontiersin.org/articles/10.3389/fped.2022.1016889/fullpulmonary hypertensionright heart failureRNA-sequencebiomarkerMKI67 |
spellingShingle | Huiling Zhou Ke Gong Yifeng Yang Qin Wu Qiuguo Wang Yadan Shen Yadan Shen Li Xie Yibo Gong Haidan Liu Haidan Liu Jijia Liu MKI67 as a potential diagnostic biomarker in pulmonary hypertension Frontiers in Pediatrics pulmonary hypertension right heart failure RNA-sequence biomarker MKI67 |
title | MKI67 as a potential diagnostic biomarker in pulmonary hypertension |
title_full | MKI67 as a potential diagnostic biomarker in pulmonary hypertension |
title_fullStr | MKI67 as a potential diagnostic biomarker in pulmonary hypertension |
title_full_unstemmed | MKI67 as a potential diagnostic biomarker in pulmonary hypertension |
title_short | MKI67 as a potential diagnostic biomarker in pulmonary hypertension |
title_sort | mki67 as a potential diagnostic biomarker in pulmonary hypertension |
topic | pulmonary hypertension right heart failure RNA-sequence biomarker MKI67 |
url | https://www.frontiersin.org/articles/10.3389/fped.2022.1016889/full |
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