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Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver Sinusoidal Endothelial Cell Dedifferentiation
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Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver Sinusoidal Endothelial Cell Dedifferentiation
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Journal Article
Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver Sinusoidal Endothelial Cell Dedifferentiation
2017
Overview
Sinusoidal dedifferentiation is a complicated process induced by several factors, and exists in early stage of diverse liver diseases. The mechanism of sinusoidal dedifferentiation is poorly unknown. In this study, we established a NaAsO
2
-induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial cells were isolated and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic approach was adopted to globally examine the effects of arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of sinusoidal dedifferentiation. In all, 4205 proteins were identified and quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were significantly changed in NaAsO
2
group, compared with the normal control. Validation by western blot showed increased level of clathrin-associated sorting protein Disabled 2 (Dab2) in NaAsO
2
group, indicating that it may regulate receptor endocytosis, which served as a mechanism to augment intracellular VEGF signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and angiogenesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 13/51
/ 13/89
/ 14/34
/ 14/35
/ 45/29
/ 64/60
/ 82/58
/ 82/80
/ Adaptor Proteins, Vesicular Transport - genetics
/ Adaptor Proteins, Vesicular Transport - metabolism
/ Animals
/ Arsenic
/ Cell Dedifferentiation - drug effects
/ Clathrin
/ Computational Biology - methods
/ Endothelial Cells - cytology
/ Endothelial Cells - drug effects
/ Endothelial Cells - physiology
/ Humanities and Social Sciences
/ Liver
/ Male
/ Mice
/ Proteome
/ Receptors, Cell Surface - metabolism
/ Science
