Dataset Information

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

ABSTRACT:

Objective

Patients with diabetes mellitus frequently have chronic wounds or diabetic ulcers as a result of impaired wound healing, which may lead to limb amputation. Human umbilical vein endothelial cell (HUVEC) dysfunction also delays wound healing. Here, we investigated the mechanism of miR-200b in HUVECs under high glucose conditions and the potential of miR-200b as a therapeutic target.

Materials and methods

In this experimental study, HUVECs were cultured with 5 or 30 mM glucose for 48 hours. Cell proliferation was evaluated by CCK-8 assays. Cell mobility was tested by wound healing and Transwell assays. Angiogenesis was analyzed in vitro Matrigel tube formation assays. Luciferase reporter assays were used to test the binding of miR-200b with Notch1.

Results

miR-200b expression was induced by high glucose treatment of HUVECs (P<0.01), and it significantly repressed cell proliferation, migration, and tube formation (P<0.05). Notch1 was directly targeted and repressed by miR-200b at both the mRNA and protein levels. Inhibition of miR-200b restored Notch1 expression (P<0.05) and reactivated the Notch pathway. The effects of miR-200b inhibition in HUVECs could be reversed by treatment with a Notch pathway inhibitor (P<0.05), indicating that the miR-200b/Notch axis modulates the proliferation, migration, and tube formation ability of HUVECs.

Conclusion

Inhibition of miR-200b activated the angiogenic ability of endothelial cells and promoted wound healing through reactivation of the Notch pathway in vitro. miR-200b could be a promising therapeutic target for treating HUVEC dysfunction.

SUBMITTER: Qiu TY

PROVIDER: S-EPMC7944128 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

Qiu Tie-Ying TY Huang Jin J Wang Li-Ping LP Zhu Bi-Song BS

Cell journal 20210301 1

<h4>Objective</h4>Patients with diabetes mellitus frequently have chronic wounds or diabetic ulcers as a result of impaired wound healing, which may lead to limb amputation. Human umbilical vein endothelial cell (HUVEC) dysfunction also delays wound healing. Here, we investigated the mechanism of miR-200b in HUVECs under high glucose conditions and the potential of miR-200b as a therapeutic target.<h4>Materials and methods</h4>In this experimental study, HUVECs were cultured with 5 or 30 mM gluc ...[more]

PMID: 33650820

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Project description:ALDH1A1 is a cytosolic enzyme upregulated in tumor cells, involved in detoxifying cells from reactive aldehydes and in acquiring resistance to chemotherapeutic drugs. Its expression correlates with poor clinical outcomes in a number of cancers, including melanoma. The present study hypothesized that the increased ALDH1A1 expression and activity upregulated the release of proangiogenic factors from melanoma cells, which regulate angiogenic features in endothelial cells (ECs) through a rearrangement of the Notch pathway. In vivo, when subcutaneously implanted in immunodeficient mice, ALDH1A1 overexpressing melanoma cells displayed a higher microvessel density. In a 3D multicellular system, obtained co‑culturing melanoma cancer cells with stromal cells, including ECs, melanoma ALDH1A1 overexpression induced the recruitment of ECs into the core of the tumorspheres. By using a genes array, overexpression of ALDH1A1 in tumor cells also promoted modulation of Notch cascade gene expression in ECs, suggesting an interaction between tumor cells and ECs mediated by enrichment of angiogenic factors in the tumor microenvironment. To confirm this hypothesis, inactivation of ALDH1A1 by the pharmacological inhibitor CM037 significantly affected the release of angiogenic factors, including IL‑8, from melanoma cells. High levels of ALDH1A1, through the retinoic acid pathway, regulated the activation of NF‑kB‑p65 and IL‑8. Further, in a 2D co‑culture system, the addition of an IL‑8 neutralizing antibody to ECs co‑cultured with melanoma cells forced to express ALDH1A1 dampened endothelial angiogenic features, both at the molecular (in terms of gene and protein expression of mediators of the Notch pathway) and at the functional level (proliferation, scratch assay, tube formation and permeability). In conclusion, these findings demonstrated the existence of a link between melanoma ALDH1A1 expression and EC Notch signaling modification that results in a pro‑angiogenic phenotype. Based on the crucial role of ALDH1A1 in melanoma control of the tumor microenvironment, the enzyme seems a promising target for the development of novel drugs able to interrupt the cross‑talk between cancer (stem) cells and endothelial cells.

Dataset Information

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

Objective

Materials and methods

Results

Conclusion

Publications

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

Similar Datasets

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