Unknown

Dataset Information

0

Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways.


ABSTRACT: Hyaluronan (HA), a large nonsulfated glycosaminogycan in the extracellular matrix, whose degraded fragments termed as low molecular weight hyaluronan (LMW-HA), has been reported as an important regulator of angiogenesis. However, little is known about the influence of LMW-HA on lymphangiogenesis. In this study, we try to explore the in vitro effects of LMW-HA on lymphangiogenesis and identify the underlying molecular mechanisms. Our results showed that LMW-HA stimulation significantly increased lymphatic endothelial cells (LECs) proliferation, migration and tube formation. Further experiments demonstrated that LMW-HA altered actin cytoskeleton rearrangement and increased the formation of intense stress fibers, lamellipodia and filopodia. Mechanistically, LMW-HA stimulation resulted in rapid tyrosine phosphorylation of protein kinase C ?/?II (PKC?/?II) and extracellular-regulated kinase 1/2 (ERK1/2). Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a homologue of CD44, is the main cell surface receptor for HA in LECs. Blocking the binding interaction of LMW-HA with LYVE-1 using neutralizing anti-LYVE-1 antibodies significantly inhibited LECs proliferation, migration, tube formation and signal transduction induced by LMW-HA, suggesting that LMW-HA may play a critical role in the processes required for lymphangiogenesis through interactions with its receptor LYVE-1 and triggering intracellular signal cascades.

SUBMITTER: Wu M 

PROVIDER: S-EPMC3965470 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5732759 | BioStudies
2006-01-01 | S-EPMC3072054 | BioStudies
1000-01-01 | S-EPMC5122770 | BioStudies
2020-01-01 | S-EPMC7152780 | BioStudies
1000-01-01 | S-EPMC5139649 | BioStudies
2018-01-01 | S-EPMC5876295 | BioStudies
1999-01-01 | S-EPMC2132933 | BioStudies
2009-01-01 | S-EPMC2665001 | BioStudies
2019-01-01 | S-EPMC6520718 | BioStudies
1000-01-01 | S-EPMC1800809 | BioStudies