Kim D K, Zhang L, Dzau V J, Pratt R E
Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94305-5246.
J Clin Invest. 1994 Jan;93(1):355-60. doi: 10.1172/JCI116967.
Vascular smooth muscle cell migration, proliferation, and differentiation are central to blood vessel development. Since neointimal formation after vascular injury may require the reexpression of a smooth muscle developmental sequence, we examined the expression of H19, a developmentally regulated gene, in rat blood vessels. Expression of the H19 gene is associated with the differentiation process that takes place during development of many tissues. Consistent with this, H19 was highly expressed in the 1-d-old rat aorta but was undetectable in the adult. H19 transcripts were only minimally detected in uninjured carotid artery but were abundant at 7 and 14 d after injury and were localized by in situ hybridization, primarily to the neointima. H19 transcript were undetectable in proliferating neointimal cells in culture but became highly abundant in postconfluent, differentiated neointimal cells. H19 transcripts were only minimally expressed in adult medial smooth muscle cells grown under the identical conditions. Thus, H19 may play an important role in the normal development and differentiation of the blood vessel and in the phenotypic changes of the smooth muscle cells, which are associated with neointimal lesion formation. The vascular injury model may be a useful system to use in examining the function of H19.
血管平滑肌细胞的迁移、增殖和分化是血管发育的核心。由于血管损伤后的新生内膜形成可能需要平滑肌发育序列的重新表达，我们检测了发育调控基因H19在大鼠血管中的表达。H19基因的表达与许多组织发育过程中发生的分化过程相关。与此一致的是，H19在1日龄大鼠主动脉中高度表达，但在成年大鼠中未检测到。H19转录本在未损伤的颈动脉中仅微量检测到，但在损伤后7天和14天大量存在，并通过原位杂交定位，主要位于新生内膜。在培养的增殖性新生内膜细胞中未检测到H19转录本，但在汇合后、分化的新生内膜细胞中变得高度丰富。在相同条件下培养的成年中膜平滑肌细胞中，H19转录本仅微量表达。因此，H19可能在血管的正常发育和分化以及与新生内膜病变形成相关的平滑肌细胞表型变化中发挥重要作用。血管损伤模型可能是用于研究H19功能的有用系统。
