Endomucin is a type I integral membrane glycoprotein,which is expressed in venous and capillary endothelial cells.It consists of 261 amino acids with an extracellular domain that is highly O-glycosylated at serine and...Endomucin is a type I integral membrane glycoprotein,which is expressed in venous and capillary endothelial cells.It consists of 261 amino acids with an extracellular domain that is highly O-glycosylated at serine and threonine residues and has several potential N-glycosylation sites.Endomucin plays an important role in biological processes such as cell interaction,molecular cell signaling,angiogenesis and cell migration,and in recent years it has also been identified as an anti-adhesion molecule and a marker of endothelial cells.While it has been shown to be involved in a number of physiological and pathological mechanisms,many of its functions remain unknown,and further study is needed.This article reviews research progress on the function of endomucin to date,in order to provide guidance for future studies.展开更多
Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues a...Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.展开更多
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2016-I2M-3-019National Science and Technology Major Project,Grant/Award Number:2017ZX10304402。
文摘Endomucin is a type I integral membrane glycoprotein,which is expressed in venous and capillary endothelial cells.It consists of 261 amino acids with an extracellular domain that is highly O-glycosylated at serine and threonine residues and has several potential N-glycosylation sites.Endomucin plays an important role in biological processes such as cell interaction,molecular cell signaling,angiogenesis and cell migration,and in recent years it has also been identified as an anti-adhesion molecule and a marker of endothelial cells.While it has been shown to be involved in a number of physiological and pathological mechanisms,many of its functions remain unknown,and further study is needed.This article reviews research progress on the function of endomucin to date,in order to provide guidance for future studies.
基金This work was supported by grants from the National Natural Science Foundation of China(31730041,31671523,and 81470416).
文摘Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.
