Zhang Jin, Perez Aymee, Yasin Mohammad, Soto Pedro, Rong Min, Theodoropoulos George, Carothers Carraway Coralie A, Carraway Kermit L
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida, USA.
J Cell Physiol. 2005 Jul;204(1):166-77. doi: 10.1002/jcp.20277.
MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP-1 (MUC4alpha) and a transmembrane subunit ASGP-2 (MUC4beta), which has been implicated in the protection of epithelial cell surfaces. Surprisingly, development and characterization of a new monoclonal antibody (mAb), called 1G8, against ASGP-2 demonstrated by immunohistochemistry the presence of MUC4 at the luminal surfaces of blood vessels of both normal tissues and tumors. Muc4 was detected with 1G8 and other Muc4 antibodies in blood vessels from humans, rats and mice. This expression of MUC4 in endothelial cells was confirmed by immunoblotting with 1G8 in human umbilical vein endothelial cells (HUVECs), human iliac artery endothelial cells (HIAECs), and human microvascular endothelial cells (HMVECs). MUC4 could be observed on HUVECs grown on either plastic or Matrigel. Finally, MUC4 expression in the three types of endothelial cell lines was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). These results provide, to our knowledge, the first demonstration of a member of the MUC gene family and membrane mucin in blood vessels. As a luminal surface component, the MUC4 is situated to contribute to the non-adhesive luminal surface and to act as an intrinsic protection and survival factor.
MUC4是一种异二聚体膜黏蛋白,由黏蛋白亚基ASGP-1(MUC4α)和跨膜亚基ASGP-2(MUC4β)组成,其与上皮细胞表面的保护有关。令人惊讶的是,一种针对ASGP-2的新型单克隆抗体(mAb)1G8的研发及特性研究表明,通过免疫组织化学法可在正常组织和肿瘤的血管腔表面检测到MUC4。利用1G8和其他Muc4抗体在人、大鼠和小鼠的血管中检测到了Muc4。通过用1G8对人脐静脉内皮细胞(HUVEC)、人髂动脉内皮细胞(HIAEC)和人微血管内皮细胞(HMVEC)进行免疫印迹,证实了MUC4在内皮细胞中的这种表达。在塑料或基质胶上生长的HUVEC上均可观察到MUC4。最后,通过逆转录-聚合酶链反应(RT-PCR)证实了三种内皮细胞系中MUC4的表达。据我们所知,这些结果首次证明了MUC基因家族的一个成员及膜黏蛋白在血管中的存在。作为腔表面成分,MUC4有助于形成非黏附性的腔表面,并作为一种内在的保护和存活因子发挥作用。