ArticleInternational journal of molecular sciences2021
CDC2 Is an Important Driver of Vascular Smooth Muscle Cell Proliferation via FOXM1 and PLK1 in Pulmonary Arterial Hypertension.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Chronic Aspartame Exposure Leading to Hypertension in Mice may be Related to the Activation of the Wnt/β-Catenin Signaling Pathway in the Hypothalamus.Molecular nutrition & food research · 2026Article
- Mangiferin in human disease: Multifaceted mechanisms and applications (Review).International journal of molecular medicine · 2026Review
- Activation of PBK by Gal-3 contributes to pulmonary artery hypertension by promoting PRC1 activation.Respiratory research · 2026Article
- Leiomodin 1 haploinsufficiency promotes smooth muscle cell proliferation and increases neointimal lesion size.Vascular pharmacology · 2025Article
- Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.Microbiology spectrum · 2025Article
- Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease.Cardiovascular diabetology · 2024Article
- A novel anoikis-related gene signature predicts prognosis in patients with sepsis and reveals immune infiltration.Scientific reports · 2024Article
- Article
- Targets for Renal Carcinoma Growth Control Identified by Screening FOXD1 Cell Proliferation Pathways.Cancers · 2022Article
- Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.Biochemical and biophysical research communications · 2022Article
- Bioinformatics Analysis Reveals Cell Cycle-Related Gene Upregulation in Ascending Aortic Tissues From Murine Models.Frontiers in genetics · 2022Article
- Inhibitors of Mitochondrial Dynamics Mediated by Dynamin-Related Protein 1 in Pulmonary Arterial Hypertension.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
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Abstract
A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein, we identify cyclin-dependent kinase 1 (CDK1), also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7, and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.
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