PDF(Pubmed)
Abstract：
KRIT1 is a 75 kDa scaffolding protein which regulates endothelial cell phenotype by limiting the response to inflammatory stimuli and maintaining a quiescent and stable endothelial barrier. Loss-of-function mutations in KRIT1 lead to the development of cerebral cavernous malformations (CCM), a disease marked by the formation of abnormal blood vessels which exhibit a loss of barrier function, increased endothelial proliferation, and altered gene expression. While many advances have been made in our understanding of how KRIT1, and the functionally related proteins CCM2 and PDCD10, contribute to the regulation of blood vessels and the vascular barrier, some important open questions remain. In addition, KRIT1 is widely expressed and KRIT1 and the other CCM proteins have been shown to play important roles in non-endothelial cell types and tissues, which may or may not be related to their role as pathogenic originators of CCM. In this review, we discuss some of the unsettled questions regarding the role of KRIT1 in vascular physiology and discuss recent advances that suggest this ubiquitously expressed protein may have a role beyond the endothelial cell.
摘要：
KRIT1是一种75kDa支架蛋白，通过限制对炎性刺激的反应并维持静止和稳定的内皮屏障来调节内皮细胞表型。KRIT1功能突变的缺失导致脑海绵状畸形（CCM）的发展，一种以异常血管形成为特征的疾病，表现出屏障功能的丧失，内皮增殖增加，和改变基因表达。虽然我们在理解KRIT1以及功能相关蛋白CCM2和PDCD10如何促进血管和血管屏障的调节方面取得了许多进展，一些重要的悬而未决的问题仍然存在。此外,KRIT1广泛表达，KRIT1和其他CCM蛋白已被证明在非内皮细胞类型和组织中起重要作用，这可能与他们作为CCM致病源的作用有关，也可能与他们的作用无关。在这次审查中,我们讨论了关于KRIT1在血管生理学中的作用的一些未解决的问题,并讨论了最近的进展,这些进展表明,这种广泛表达的蛋白可能具有超出内皮细胞的作用.
