Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain
Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.
EMBO Mol Med. 2017 Oct;9(10):1338-1345. doi: 10.15252/emmm.201707950.
The discovery of a mutation in a specific gene can be very important for determining the pathophysiology underlying the disease of a patient and may also help to decide the best treatment protocol on an individual basis. However, sometimes the discovery of mutations in new proteins advances our comprehension in a more widespread manner. The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is fundamental for systemic growth, but is also involved in many other important processes. Our understanding of this system in physiology and pathophysiology has advanced throughout the years with each discovery of mutations in members of this axis. This review focuses on the most recent discovery: mutations in the metalloproteinase pregnancy-associated plasma protein-A2 (PAPP-A2), one of the proteases involved in liberating IGF-1 from the complexes in which it circulates, in patients with delayed growth failure. We also discuss the advances in the stanniocalcins (STC1 and STC2), proteins that modulate PAPP-A2, as well as PAPP-A. These new advances not only bring us one step closer to understanding the strict spatial and temporal control of this axis in systemic growth and maturation, but also highlight possible therapeutic targets when this system goes awry.
特定基因突变的发现对于确定患者疾病的病理生理学基础非常重要，也有助于根据个体情况决定最佳治疗方案。然而，有时新蛋白质突变的发现会以更广泛的方式促进我们的理解。生长激素（GH）/胰岛素样生长因子（IGF）-1 轴对于全身生长至关重要，但也参与许多其他重要过程。随着该轴成员突变的每一次发现，我们对该系统的生理学和病理生理学的理解都在不断进步。这篇综述重点介绍了最近的发现：在生长迟缓的患者中，与 IGF-1 从其循环复合物中释放有关的蛋白酶之一，金属蛋白酶妊娠相关血浆蛋白-A2（PAPP-A2）的突变。我们还讨论了调节 PAPP-A2 的 STC 蛋白（STC1 和 STC2）以及 PAPP-A 的进展。这些新进展不仅使我们更接近于理解该轴在全身生长和成熟中的严格时空控制，而且当该系统出现异常时，还突出了可能的治疗靶点。
