Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Am J Physiol Cell Physiol. 2021 Jan 1;320(1):C106-C118. doi: 10.1152/ajpcell.00366.2020. Epub 2020 Oct 28.
Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular diseases, and kidney disorders are intensively studied to find effective therapeutic targets. Given the serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin has been associated with diverse pathophysiological events. In particular, we focus here on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.
丝氨酸蛋白酶抑制剂是一类具有共同功能的蛋白质超家族，其特征为丝氨酸蛋白酶抑制剂。迄今为止，已经从九个分支鉴定出 36 种丝氨酸蛋白酶抑制剂。这些蛋白质在所有器官中表达，并参与多种重要功能，如血压调节、激素运输、胰岛素敏感性和炎症反应。肥胖症、糖尿病、心血管疾病和肾脏疾病等疾病被深入研究，以寻找有效的治疗靶点。鉴于丝氨酸蛋白酶抑制剂的出色功能，某些类型的丝氨酸蛋白酶抑制剂的缺乏或过表达与多种病理生理事件有关。在这里，我们特别关注研究丝氨酸蛋白酶抑制剂，特别是 SerpinA3，在发生在相关器官如大脑、视网膜、角膜、肺、心脏血管和肾脏中的多种疾病中的参与。在这篇综述中，我们总结了丝氨酸蛋白酶抑制剂在生理和病理生理过程中的作用，以及 SerpinA3 在几种病理中的关键作用的最新证据。最后，我们强调了 SerpinA3 在调节细胞过程如血管生成、细胞凋亡、纤维化、氧化应激和炎症反应中的重要性。
