The role of the microRNA-126 in lymphangiogenesis
Abstract/Contents
- Abstract
- The lymphatic vasculature (LV) is an essential component of the cardiovascular system and fulfills critical roles during development and in the pathogenesis of diseases such as lymphedema, cancer metastasis and various inflammatory conditions. Although, there has been progress in the field of lymphatic vascular research, our understanding of lymphatic vessel development and pathogenesis is still rather limited. We have previously shown that the endothelial-specific microRNA-126 plays a crucial role in mediating developmental angiogenesis in vivo. In this study we demonstrate that miR-126 is also necessary for the formation of de novo lymphangiogenesis. To this extent, we have employed an in vivo approach by utilizing our miR-126 knockout (KO) mice as well as lymphatic specific driver mice (Prox1CreERT2) to address the role of miR-126 in the lymphatic vasculature. Regulation of lymphangiogenesis by miR-126 was confirmed using sophisticated in vivo models such as the tail lymphedema, corneal micropocket assay and intradermal injections with adenovirus encoding VEGF-C (VEGF-C challenge). In vitro studies have shown that miR-126 is highly expressed in both human and mouse lymphatic endothelial cells (LECs). MiR-126 knockdown in HLECs results in reduced proliferation and decreased cell viability with abrupt VEGF-C removal. Furthermore, VEGF-C induces miR-126 expression in a dose-dependent manner, suggesting that there is a molecular link between miR-126 and the VEGFR-3/VEGF-C signaling pathway. Our studies show that miR-126 can play a dual role not only in regulating angiogenesis but also lymphangiogenesis in vivo. Understanding the role of miR-126 in lymphangiogenesis provides further insight for the therapeutic manipulation of lymphatic vessels. Overall, this thesis has unveiled a novel role for miR-126 in lymphangiogenesis. Future studies are needed to elucidate the precise mechanism of action of miR-126 in this context are needed and are currently ongoing. It is our hope that gaining a deep understanding of how miR-126 regulates lymphatic endothelial cell physiology will provide valuable contributions towards improving our ability to treat cancer metastasis through manipulation of its principal dissemination avenue, the lymphatic vasculature.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Reyes, Teresa F | |
|---|---|---|
| Associated with | Stanford University, Cancer Biology Program. | |
| Primary advisor | Kuo, Calvin Jay | |
| Primary advisor | Rockson, Stanley G | |
| Thesis advisor | Kuo, Calvin Jay | |
| Thesis advisor | Rockson, Stanley G | |
| Thesis advisor | Giaccia, Amato J | |
| Thesis advisor | Lipsick, Joseph Steven, 1955- | |
| Advisor | Giaccia, Amato J | |
| Advisor | Lipsick, Joseph Steven, 1955- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Teresa F. Reyes. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Teresa Reyes
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