TBX20 and the PROK2-PROKR1 pathway—new kid on the block in angiogenesis research

Lichtenauer, Michael; Jung, Christian

doi:10.21037/atm.2018.08.41

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…KLKB1 is usually synthesized in hepatocytes and secreted into the blood and is involved in the surface-dependent activation of blood coagulation, fibrinolysis, kinin production, and biological processes of inflammation, which can reflect the severity of liver injury (Che et al, 2021). The TBX20-PROK2-PROKR1 pathway may also be a target for the treatment of diseases associated with dysregulation of angiogenesis, benefit on patients with ischemic heart failure (Lichtenauer and Jung, 2018). Comparisons with similar studies might involve investigations into other receptor genes, such as PROK2 (Lichtenauer and Jung, 2018), EDN1 (Liang et al, 2018), and NOS3 (Teralı and Ergören, 2019), which play roles in vascular function and inflammation regulation and may have similar implications in CAD.…”

Section: Discussionmentioning

confidence: 99%

“…The TBX20-PROK2-PROKR1 pathway may also be a target for the treatment of diseases associated with dysregulation of angiogenesis, benefit on patients with ischemic heart failure (Lichtenauer and Jung, 2018). Comparisons with similar studies might involve investigations into other receptor genes, such as PROK2 (Lichtenauer and Jung, 2018), EDN1 (Liang et al, 2018), and NOS3 (Teralı and Ergören, 2019), which play roles in vascular function and inflammation regulation and may have similar implications in CAD.…”

Section: Discussionmentioning

confidence: 99%

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Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease

Zheng,

Li,

Xiong

2024

Front. Genet.

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Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease and cause significant morbidity and mortality. Abnormal coagulation cascade is one of the high-risk factors in CAD patients, but the molecular mechanism of coagulation in CAD is still limited.Methods: We clustered and categorized 352 CAD paitents based on the expression patterns of coagulation-related genes (CRGs), and then we explored the molecular and immunological variations across the subgroups to reveal the underlying biological characteristics of CAD patients. The feature genes between CRG-subgroups were further identified using a random forest model (RF) and least absolute shrinkage and selection operator (LASSO) regression, and an artificial neural network prediction model was constructed.Results: CAD patients could be divided into the C1 and C2 CRG-subgroups, with the C1 subgroup highly enriched in immune-related signaling pathways. The differential expressed genes between the two CRG-subgroups (DE-CRGs) were primarily enriched in signaling pathways connected to signal transduction and energy metabolism. Subsequently, 10 feature DE-CRGs were identified by RF and LASSO. We constructed a novel artificial neural network model using these 10 genes and evaluated and validated its diagnostic performance on a public dataset.Conclusion: Diverse molecular subgroups of CAD patients may each have a unique gene expression pattern. We may identify subgroups using a few feature genes, providing a theoretical basis for the precise treatment of CAD patients with different molecular subgroups.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease

Zheng,

Li,

Xiong

2024

Front. Genet.

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“…Angiogenesis, a process of blood vessel formation from pre-existing vascular structures, has a pivotal impact on human health and the pathological process of many diseases, such as female menstrual cycle, tissue growth, wound healing, cancer, ischemia, inflammatory diseases, and blinding eye diseases [1]. The process of angiogenesis is extremely complicated and dynamic, which includes endothelial cells transition from resting to activated state, new capillary tube formation, vascular elongation, further sprouting, and remodeling [2,3]. Angiogenesis is triggered by growth factors and tightly regulated by signaling pathways [4,5].…”

Section: Introductionmentioning

confidence: 99%

1,6-Hexanediol regulates angiogenesis via suppression of cyclin A1-mediated endothelial function

et al. 2023

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Background Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid–liquid phase separation (LLPS) has emerged as a new concept to explain many cellular functions and diseases. However, whether LLPS is involved in angiogenesis has not been studied until now. Here, we investigated the potential role of LLPS in angiogenesis and endothelial function. Results We found 1,6-hexanediol (1,6-HD), an inhibitor of LLPS, but not 2,5-hexanediol (2,5-HD) dramatically decreases neovascularization of Matrigel plug and angiogenesis response of murine corneal in vivo. Moreover, 1,6-HD but not 2,5-HD inhibits microvessel outgrowth of aortic ring and endothelial network formation. The endothelial function of migration, proliferation, and cell growth is suppressed by 1,6-HD. Global transcriptional analysis by RNA-sequencing reveals that 1,6-HD specifically blocks cell cycle and downregulates cell cycle-related genes including cyclin A1. Further experimental data show that 1,6-HD treatment greatly reduces the expression of cyclin A1 but with minimal effect on cyclin D1, cyclin E1, CDK2, and CDK4. The inhibitory effect of 1,6-HD on cyclin A1 is mainly through transcriptional regulation because proteasome inhibitors fail to rescue its expression. Furthermore, overexpression of cyclin A1 in HUVECs largely rescues the dysregulated tube formation upon 1,6-HD treatment. Conclusions Our data reveal a critical role of LLPS inhibitor 1,6-HD in angiogenesis and endothelial function, which specifically affects endothelial G1/S transition through transcriptional suppression of CCNA1, implying LLPS as a possible novel player to modulate angiogenesis, and thus, it might represent an interesting therapeutic target to be investigated in clinic angiogenesis-related diseases in future.

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“…PROK1 acts on two G protein‐coupled receptors, namely prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). Activation of PKR1 induces the angiogenic function, whilst PKR2 activation mediates the cell permeability and anti‐apoptosis effects 41 . Due to the fact that angiogenesis is essential for tumour growth and metastasis, the presence and role of PKR1 in exosomes isolated from cultured ovarian cancer cells is concerned in this study.…”

Section: Introductionmentioning

confidence: 99%

Ovarian cancer derived PKR1 positive exosomes promote angiogenesis by promoting migration and tube formation in vitro

Zhang

Sheng

et al. 2020

Cell Biochemistry & Function

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Cancer cell derived exosomes play important roles in cancer progression and modulation of the tumour microenvironment. This study aims to investigate the role of prokineticin receptor 1 (PKR1) positive exosomes on angiogenesis. In the present study, PKR1 expression in tumour samples from ovarian cancer patients were examined firstly. Then, two ovarian cancer cell lines, namely A2780 and HO‐8910 cells, were used to isolate and obtain the PKR1 positive exosomes from the serum free medium. The function analysis of PKR1 positive exosomes on angiogenesis was conducted by cell proliferation and migration assay, tube formation analysis, and tumour volume assay. The results showed that PKR1 expression was down regulated in tumour samples of ovarian cancer patients compared with adjacent normal tissues. The intracellular expression of PKR1 could be detected in A2780 and HO‐8910 cells. And, the isolated exosomes from the serum free medium were confirmed by transmission electron microscopic and NTA analysis, as well as the co‐presence of PKR1 with exosome marker CD63. The function analysis of PKR1 positive exosomes on angiogenesis demonstrated the uptake of PKR1 positive exosomes by human umbilical vein endothelial cells through immunofluorescence staining. The angiogenesis assays in vitro indicated that PKR1 positive exosomes promoted migration and tube formation of HUVECs but not proliferation. The endogenous PKR1 was also verified to help to enhance migration and promote tube formation of vascular endothelial cells, which might involved in the phosphorylation of STAT3. Additionally, The tumour volume from exosomes treated A2780 tumour‐bearing mice was significantly increased compared with the control group, accompanied with the induced PKR1 expression and phosphorylation of STAT3 level. Significance of the Study This study proved the important role of PKR1 positive exosomes released from ovarian cancer cells on promoting angiogenesis. The data indicated that PKR1 derived from ovarian cancer cells could act as an important tumour associated antigen and biomolecular factor for cellular communication in tumour microenvironment.

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TBX20 and the PROK2-PROKR1 pathway—new kid on the block in angiogenesis research

Cited by 7 publications

References 19 publications

Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease

Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease

1,6-Hexanediol regulates angiogenesis via suppression of cyclin A1-mediated endothelial function

Ovarian cancer derived PKR1 positive exosomes promote angiogenesis by promoting migration and tube formation in vitro

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