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Updated: Dec 15, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-375-3p regulates rat pulmonary microvascular endothelial cell activity by targeting Notch1 during hypoxia
Yuan An1,2, Ziquan Liu3, Hui Ding4
1Tianjin Medical University, Tianjin, P. R. China.
Objective:
Pulmonary microvascular endothelial cells (PMECs) exhibit specific responses in adaptation to hypoxia. However, the mechanisms regulating PMEC activities during hypoxia remain unclear. This study investigated the potential involvement of a microRNA, miR-375-3p, in the regulation of PMEC activities.
Methods:
Primary PMECs were isolated from rats. The expression levels of miR-375-3p and Notch1 in the PMECs were detected by quantitative PCR and western blotting. Luciferase reporter assays were performed to explore the transcriptional regulation of Notch1 by miR-375-3p. The proliferation and chemotaxis of the PMECs were measured with the Cell Counting Kit-8 and Transwell invasion assays, respectively. Additionally, the capacity of hypoxia-treated PMECs for angiogenesis and inflammatory response was determined with tube formation assays and ELISA, respectively.
Results:
The expression of miR-375-3p and Notch1 in the PMECs was significantly down-regulated and up-regulated during hypoxia, respectively. The results demonstrated that miR-375-3p directly targets Notch1 in PMECs, thereby suppressing the transcriptional expression of Notch1. It was further revealed that miR-375-3p regulates the proliferation, chemotaxis, angiogenesis, and inflammatory response of PMECs.
Conclusions:
Our findings revealed the important role of miR-375-3p in the regulation of PMEC function and suggest the potential involvement of miR-375-3p in the development of lung diseases.
Insights
MicroRNA miR-375-3p regulates pulmonary microvascular endothelial cell (PMEC) function during hypoxia by targeting Notch1. This finding offers potential insights into lung disease development.
Area of Science:
- Pulmonary vascular biology
- Molecular regulation of cellular function
Background:
- Pulmonary microvascular endothelial cells (PMECs) adapt to hypoxia through specific responses.
- Mechanisms controlling PMEC activity during hypoxia are not fully understood.
Purpose of the Study:
- To investigate the role of microRNA miR-375-3p in regulating PMEC activities under hypoxic conditions.
Main Methods:
- Quantitative PCR and western blotting to assess miR-375-3p and Notch1 expression.
- Luciferase reporter assays to confirm direct targeting of Notch1 by miR-375-3p.
- Functional assays including proliferation, chemotaxis, angiogenesis, and inflammatory response measurements.
Main Results:
- Hypoxia led to decreased miR-375-3p and increased Notch1 expression in PMECs.
- miR-375-3p was found to directly suppress Notch1 transcription.
- miR-375-3p significantly influenced PMEC proliferation, chemotaxis, angiogenesis, and inflammatory responses.
Conclusions:
- miR-375-3p plays a crucial role in regulating PMEC function.
- miR-375-3p may be implicated in the pathogenesis of lung diseases.
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