The epithelial junction protein MarvelD3 in cell proliferation and migration

上皮细胞是连续的细胞层，划分我们的组织和器官。单个上皮细胞通过介导粘附的分子复合物相互作用，但也作为传感器将有关环境的信息（如邻近细胞的存在或不存在）传递到细胞内部。上皮的完整性对于我们器官的正常发育和功能，以及保护我们免受环境的影响是很重要的。例如，皮肤等上皮层或肠道内壁的破裂可导致严重感染，并可能由于慢性炎症或病毒和细菌的急性感染而发生。同样，癌细胞的一个特征是它们失去了感知邻近细胞存在的能力，因此它们继续在邻近细胞的上面增殖和迁移，或者通过迁移和侵入其他组织和器官而离开它们的起源组织，从而形成转移。另一方面，在许多成人组织中，细胞不再繁殖，这可能导致细胞数量减少，并由于年龄或组织损伤而失去正常的器官功能。因此，了解组织中的细胞是如何相互粘附和识别的，这是如何影响它们的增殖和迁移特性的，以及我们如何利用这种机制来操纵它们的行为来解决医疗问题，这是至关重要的。在这里，我们提出实验来研究一种新的机制，基于我们未发表的结果，将细胞之间的粘附与细胞迁移和增殖的调节联系起来。我们的第一个目标是确定这种机制在上皮修复过程中如何起作用，我们的第二个目标是确定它如何促进上皮组织的正常发育。我们的第三个目标是利用这些信息，解决由细胞增殖不足引起的医疗问题。角膜是眼睛前部的组织，是维持正常视力所必需的。它是由外部的上皮和内部的一层称为角膜内皮的细胞组成的。由于角膜内皮细胞通常不会增殖和再生，它们的数量会随着年龄增长或角膜受损而减少。如果它们的数量过低，角膜就会失去透明度，导致视力丧失。这严重影响了用于治疗眼表损伤患者的捐献角膜移植的可用性和质量。因此，我们提出实验来测试是否可以利用本文确定的机制来提高捐献的人类角膜的质量，从而增加适合移植的角膜的数量。了解细胞如何感知它们的邻居并将这些信息传递到细胞内部，以及我们如何操纵这些过程，除了我们将在这里测试的之外，还有广泛的潜在应用。预期的结果将帮助我们想出新的方法来帮助手术后的伤口修复，并治疗慢性炎症、某些感染和癌症等破坏性疾病。

Epithelia are continuous layers of cells that delineate our tissues and organs. Individual epithelial cells interact with each other via molecular complexes that mediate adhesion but also function as sensors that transmit information about the environment, such as the presence or absence of neighbouring cells, to the cell interior. Integrity of epithelia is important for our organs to develop and function normally, and to protect us from our environment. For example, breaches in epithelial layers such as the skin or in the lining of the intestine can lead to serious infections and can occur due to chronic inflammations or acute infections by viruses and bacteria. Similarly, a characteristic of cancer cells is that they have lost the capability to sense the presence of neighbouring cells and hence continue to proliferate and migrate on top of their neighbours, or leave their tissue of origin by migrating to and invading other tissues and organs and, thereby form metastasis. On the other hand, in many adult tissues cells do no longer multiply and this can lead to reduced cell numbers and loss of normal organ function due to age or tissue damage. It is thus of fundamental importance to understand how cells in a tissue adhere to and recognise each other, how this influences their proliferative and migratory properties, and how we can exploit such mechanisms to manipulate their behaviour to address medical problems. Here we propose experiments to investigate a new mechanism that, based on our unpublished results, links adhesion between cells to the regulation of cell migration and proliferation. Our first aim is to determine how this mechanism works during epithelial repair processes and, our second aim, how it contributes to normal development of epithelial tissues. Our third aim is to use this information and address a medical problem that is caused by a lack of cell proliferation. The cornea is a tissue at the front of the eye that is required for normal vision. It is formed by an epithelium on the outside and a layer of cells on the inside, called corneal endothelium. As cells in the corneal endothelium do normally not proliferate and regenerate, their numbers decline with age or when the cornea gets damaged. If their numbers are too low, the cornea loses its transparency resulting in a loss of vision. This seriously affects the availability and quality of human corneas for transplantation that are donated to treat patients with damage to the surface of the eye. Hence, we propose experiments to test whether the here-identified mechanism can be exploited to enhance the quality of donated human corneas and thereby enhance the number of corneas that are adequate for transplantation. Knowledge of how cells sense their neighbours and transmit such information to the cell interior, and how we can manipulate such processes has a wide range of potential applications apart from the one that we will test here. The expected results will help us to think of new ways to aid wound repair after surgery and to treat devastating diseases such as chronic inflammations, certain infections and cancer.