Role of Chromogranin A and its derived peptides in the context of gut physiology

胃肠道的功能部分是由胃肠道系统内各种细胞类型产生和释放的肽激素调控的。尽管关于多肽在肠道生物学中的作用已经积累了丰富的知识，但几乎可以肯定的是，在肠道中还有其他具有重要生理活性的多肽。肠道的主要功能是吸收和推进膳食营养，但它也形成了一个物理和免疫屏障。在过去的十年里，一种新的蛋白质，最初是在肾上腺中发现的，已经彻底改变了我们对免疫系统的神经内分泌调节的看法。这种名为Chromogranin (Cg) A的新颗粒蛋白已经定义了神经内分泌和生理机制调控的新范式。颗粒蛋白家族存在于存在于肠道水平的一些神经元的染色质颗粒中，以及存在于肠壁的特定类型的内分泌、免疫和神经内分泌细胞中。细胞和组织特异性CgA已在胃肠道中被描述，产生小肽。然而，目前还不完全清楚哪些特定的小肽存在于肠道水平，以及它们如何影响胃肠道生理功能，特别是平滑肌收缩和通透性。在本研究项目中，我们建议扩展我们的知识来阐明这些肽的存在和生理作用，重点关注它们对肠道平滑肌收缩和跨上皮通透性的潜在调节。我们相信这些创新和新颖的研究将使我们扩大对cga衍生肽介导的通透性和平滑肌功能的细胞和分子机制的了解，解释细胞功能的关键调节作用，并有助于理解神经内分泌肽在肠道生理学中的作用。这将对肠道生理学产生重大影响，因为它将为其他团队更深入地描述CgA细胞与细胞内途径之间的相互作用开辟新的途径

Functions of the gastrointestinal (GI) tract are in part orchestrated by a host of peptide hormones produced and released from various cell types within the GI system. Despite the wealth of knowledge accumulated on the role of peptides in gut biology, it is almost certain that there are additional peptides with significant physiological activities in gut. The primary function of the intestine is the absorption and propulsion of dietary nutrients, but it also forms a physical and immunological barrier. During the last decade, a new type of protein, discovered initially at the adrenal gland, has revolutionized our thinking of the neuroendocrine regulation of the immune system. This new granin protein called Chromogranin (Cg) A has defined a new paradigm on how neuroendocrine and physiological mechanisms are regulated. The granin family of proteins is stored in chromaffin granules of some neurons present in the gut level, as well as specific types of endocrine, immune and neuroendocrine cells present at the gut wall. Cell and tissue specific CgA has been described in the GI tract, generating small peptides. However, it is not fully understood which specific small peptides are present at the gut level and how they affect gastrointestinal physiological functions, in particular smooth muscle contraction and permeability. In this research program, we propose to extend our knowledge to elucidate the presence and the physiological actions of these peptides, with a focus on their potential regulation of gut smooth muscle contraction and trans-epithelial permeability. We believe that these innovative and novel studies will allow us to expand our knowledge of the cellular and molecular mechanism involved in CgA-derived peptides mediated permeability and smooth muscle functions, explain roles as a key regulators of cellular function and help understand the role of neuroendocrine peptides on gut physiology. This will have a great impact in gut physiology as it will open new avenues for other teams to describe in a deeper approach the interaction between CgA cells and intracellular pathways.**