Novel G-protein coupled receptors LGR7 and LGR8; the receptors for relaxin and insulin-like peptide 3 (INSL3)

新型G蛋白偶联受体LGR7和LGR8；

• 批准号: nhmrc : 300012
• 负责人: Prof Geoffrey Tregear
• 金额: $ 33.11万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-g-protein-3-insl3/95831
• 关键词: Novel; protein; coupled; receptors; LGR7

Relaxin is a hormone which has long been known to have essential roles in pregnancy and birth. However it has also been demonstrated to have far broader involvement in the functioning of the kidney, heart and central nervous system. Furthermore, mice lacking relaxin show increased collagen, or fibrosis, in their internal organs and skin as they age. This progressive fibrosis leads to problems with bodily functions. Treatment of these mice with relaxin reverses the fibrosis and restores function, hence relaxin has great potential as a treatment for fibrotic diseases. Anti-fibrotic drugs are a major target for drug companies as suitable compounds are not currently available. Research into the mechanisms whereby relaxin exerts its cellular effects has been limited by the inability of researchers to identify its receptor. We now know that relaxin acts through a novel G-protein coupled receptor (GPCR) LGR7 and will also act on a related receptor LGR8. The LGR8 receptor is actually the receptor for a hormone with similarities to relaxin, INSL3. It is essential that an appreciation of relaxin receptor function is obtained not only for its important actions in pregnancy, but also for its clinical applications. In this regard, improved understanding of how relaxin interacts with these two receptors is essential. We will use our expertise in producing these hormones together with molecular techniques to produce the receptor, to study the interaction of relaxin and INSL3 with these receptors and the subsequent cellular events that occur. Furthermore, to more effectively use relaxin as a drug, we need to discover a smaller, more potent and orally active form of the hormone. We will develop novel technologies to aid in the discovery of the next generation of relaxin drugs. This multi-disciplinary approach will allow us to fully maximise the clinical potential of this enigmatic hormone.

松弛素是一种激素，长期以来一直被认为在怀孕和分娩中发挥重要作用。然而，它也被证明在肾脏，心脏和中枢神经系统的功能中具有更广泛的参与。此外，缺乏松弛素的小鼠随着年龄的增长，其内脏和皮肤中的胶原蛋白或纤维化增加。这种进行性纤维化导致身体功能的问题。用松弛素治疗这些小鼠可逆转纤维化并恢复功能，因此松弛素具有治疗纤维化疾病的巨大潜力。抗纤维化药物是制药公司的主要目标，因为目前还没有合适的化合物。松弛素发挥其细胞效应的机制研究一直受到研究人员无法识别其受体的限制。我们现在知道松弛素通过一种新的G蛋白偶联受体（GPCR）LGR 7起作用，也会作用于相关受体LGR 8。LGR 8受体实际上是一种与松弛素INSL 3相似的激素的受体。松弛素受体的功能不仅在妊娠中起重要作用，而且对于其临床应用也至关重要。在这方面，更好地了解松弛素如何与这两种受体相互作用是必不可少的。我们将利用我们在生产这些激素方面的专业知识以及分子技术来生产受体，研究松弛素和INSL 3与这些受体的相互作用以及随后发生的细胞事件。此外，为了更有效地使用松弛素作为药物，我们需要发现一种更小，更有效和口服活性形式的激素。我们将开发新技术，以帮助发现下一代松弛素药物。这种多学科的方法将使我们能够充分发挥这种神秘激素的临床潜力。