Han D K, Khaing Z Z, Pollock R A, Haudenschild C C, Liau G
Department of Molecular Biology, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
J Clin Invest. 1996 Mar 1;97(5):1276-85. doi: 10.1172/JCI118543.
H19 is a developmentally regulated gene with putative tumor suppressor activity, and loss of H19 expression may be involved in Wilms' tumorigenesis. In this report, we have performed in situ hybridization analysis of H19 expression during normal rabbit development and in human atherosclerotic plaques. We have also used cultured smooth muscle cells to identify H19 regulatory factors. Our data indicate that H19 expression in the developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. Expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. In the prenatal blood vessel, H19 expression was both temporally and spatially regulated with initial loss of expression in the inner smooth muscle layers adjacent to the lumen. We also identified H19-positive cells within the adult atherosclerotic lesion and we suggest that these cells may recapitulate earlier developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provide additional clues toward understanding the physiological regulation and function of H19.
H19是一个具有假定肿瘤抑制活性且受发育调控的基因，H19表达缺失可能参与肾母细胞瘤的发生。在本报告中，我们对正常兔发育过程以及人类动脉粥样硬化斑块中H19的表达进行了原位杂交分析。我们还利用培养的平滑肌细胞来鉴定H19调控因子。我们的数据表明，发育中的骨骼肌和平滑肌中H19的表达与这些组织中的特定分化事件相关。骨骼肌中H19的表达与非增殖性、肌动蛋白阳性的肌细胞相关。在产前血管中，H19的表达在时间和空间上均受到调控，最初在靠近管腔的内平滑肌层中表达缺失。我们还在成人动脉粥样硬化病变中鉴定出H19阳性细胞，我们认为这些细胞可能重现了早期的发育事件。这些结果，连同将胰岛素生长因子家族鉴定为H19表达的有效调控分子，为理解H19的生理调控和功能提供了更多线索。
