PODOPLANIN REGULATION OF LYMPHATIC ENDOTHELIAL CELL IDENTITY IN VIVO

Podoplanin 对体内淋巴内皮细胞身份的调节

• 批准号: 8364978
• 负责人: Lijun Xia
• 金额: $ 24.06万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364978
• 关键词: Biology; Blood; Blood Vessels; Cell Line; Cell Lineage; Development; Embryo; Endothelial Cells; Exhibits; Funding; Grant; Hemangiosarcoma; Interdisciplinary Study; Lymphatic Endothelial Cells; Lymphatic System; Lymphatic vessel; Maintenance; Malignant - descriptor; Mus; National Center for Research Resources; Phenotype; Principal Investigator; Process; Regulation; Research; Research Infrastructure; Resources; Source; Staging; Testing; Time; Transgenic Organisms; United States National Institutes of Health; Vascular System; cost; in vivo; podoplanin; postnatal; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The lymphatic system originates from the blood vascular system. Lymphatic endothelial cells (LECs) differentiate from blood endothelial cells (BECs), and this lineage decision as well as the maintenance of the LEC phenotype are tightly controlled processes, which is essential for development and functions of the two discrete vascular compartments. The transcription factor Prox1 is a binary regulator that promotes LEC lineage identity and suppresses BEC phenotype. However, how it functions is not well understood. We observed that mice lacking podoplanin, which is highly expressed in LECs, exhibit blood-filled lymphatic vessels that closely resemble those seen in time-specific deletion of Prox1 (inducible Prox1/) mice. We hypothesize that podoplanin, like Prox1, is critical in regulating endothelial cell identity. To test this, we propose two aims. Aim 1 will determine the embryonic and postnatal stages at which podoplanin controls LEC identity using mice with time-specific podoplanin deficiency in endothelial cells. Aim 2 will determine whether forced expression of podoplanin suppresses BEC identity in vivo using a transgenic line that over-expresses podoplanin in BECs and LECs (TetO-PdpnEC). Increased expression of Prox1 and podoplanin is associated with malignant transformation of BEC-derived angiosarcoma with a mixed BEC and LEC identity. We will investigate whether over-expression of podoplanin in endothelial cell lines (EOMA and Py-4-1) induces formation of aggressive angiosarcoma in vivo.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 淋巴系统起源于血管系统。淋巴管内皮细胞（Lymphatic endothelial cells，LEC）是从血液内皮细胞（blood endothelial cells，BECs）分化而来的，其分化过程和表型的维持是严格控制的，对两个独立的血管区室的发育和功能至关重要。转录因子Prox 1是促进LEC谱系身份和抑制BEC表型的二元调节因子。然而，它是如何运作的还不清楚。我们观察到，缺乏podoplanin（在LEC中高度表达）的小鼠表现出充满血液的淋巴管，与Prox 1（诱导型Prox 1）时间特异性缺失中所见的淋巴管非常相似。/）小鼠。我们推测，podoplanin，像Prox 1，是至关重要的调节内皮细胞的身份。 为了验证这一点，我们提出了两个目标。目的1将确定在胚胎和出生后阶段podoplanin控制LEC身份与时间特异性podoplanin缺乏内皮细胞的小鼠。目的2将使用在BEC和LEC中过表达podoplanin的转基因系（TetO-PdpnEC）确定podoplanin的强制表达是否在体内抑制BEC身份。Prox 1和podoplanin表达增加与BEC和LEC混合身份的BEC衍生血管肉瘤的恶性转化相关。我们将研究是否podoplanin在内皮细胞系（EOMA和Py-4-1）的过度表达诱导体内侵袭性血管肉瘤的形成。