Low Molecular Weight Hyaluronan Induces Lymphangiogenesis through LYVE-1-Mediated Signaling PathwaysReport as inadecuate




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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 α-βII PKCα-βII and extracellular-regulated kinase 1-2 ERK1-2. Lymphalic vessel endotheilial 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.



Author: Man Wu , Yan Du , Yiwen Liu, Yiqing He, Cuixia Yang, Wenjuan Wang, Feng Gao

Source: http://plos.srce.hr/



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