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Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading.

Publication ,  Journal Article
Tian, H; Ketova, T; Hardy, D; Xu, X; Gao, X; Zijlstra, A; Blobe, GC
Published in: Arterioscler Thromb Vasc Biol
June 2017

OBJECTIVE: Endoglin, a transforming growth factor-β superfamily coreceptor, is predominantly expressed in endothelial cells and has essential roles in vascular development. However, whether endoglin is also expressed in vascular smooth muscle cells (VSMCs), especially in vivo, remains controversial. Furthermore, the roles of endoglin in VSMC biology remain largely unknown. Our objective was to examine the expression and determine the function of endoglin in VSMCs during angiogenesis. APPROACH AND RESULTS: Here, we determine that endoglin is robustly expressed in VSMCs. Using CRISPR/CAS9 knockout and short hairpin RNA knockdown in the VSMC/endothelial coculture model system, we determine that endoglin in VSMCs, but not in endothelial cells, promotes VSMCs recruitment by the endothelial cells both in vitro and in vivo. Using an unbiased bioinformatics analysis of RNA sequencing data and further study, we determine that, mechanistically, endoglin mediates VSMC recruitment by promoting VSMC migration and spreading on endothelial cells via increasing integrin/FAK pathway signaling, whereas endoglin has minimal effects on VSMC adhesion to endothelial cells. In addition, we further determine that loss of endoglin in VSMCs inhibits VSMC recruitment in vivo. CONCLUSIONS: These studies demonstrate that endoglin has an important role in VSMC recruitment and blood vessel maturation during angiogenesis and also provide novel insights into how discordant endoglin function in endothelial and VSMCs may regulate vascular maturation and angiogenesis.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

June 2017

Volume

37

Issue

6

Start / End Page

1115 / 1126

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • RNA Interference
  • Phenotype
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Inbred C57BL
  • Integrins
  • Humans
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tian, H., Ketova, T., Hardy, D., Xu, X., Gao, X., Zijlstra, A., & Blobe, G. C. (2017). Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading. Arterioscler Thromb Vasc Biol, 37(6), 1115–1126. https://doi.org/10.1161/ATVBAHA.116.308859
Tian, Hongyu, Tatiana Ketova, Duriel Hardy, Xiaojiang Xu, Xia Gao, Andries Zijlstra, and Gerard C. Blobe. “Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading.Arterioscler Thromb Vasc Biol 37, no. 6 (June 2017): 1115–26. https://doi.org/10.1161/ATVBAHA.116.308859.
Tian H, Ketova T, Hardy D, Xu X, Gao X, Zijlstra A, et al. Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1115–26.
Tian, Hongyu, et al. “Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading.Arterioscler Thromb Vasc Biol, vol. 37, no. 6, June 2017, pp. 1115–26. Pubmed, doi:10.1161/ATVBAHA.116.308859.
Tian H, Ketova T, Hardy D, Xu X, Gao X, Zijlstra A, Blobe GC. Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1115–1126.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

June 2017

Volume

37

Issue

6

Start / End Page

1115 / 1126

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • RNA Interference
  • Phenotype
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Inbred C57BL
  • Integrins
  • Humans
  • Gene Expression Regulation