Department of Medicine, School of Medicine, University of California, San Diego, California; Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico city, Mexico.
Department of Medicine, School of Medicine, University of California, San Diego, California.
Transl Res. 2020 Aug;222:41-55. doi: 10.1016/j.trsl.2020.03.008. Epub 2020 Mar 16.
The development of organ fibrosis has garnered rising attention as multiple diseases of increasing and/or high prevalence appear to progress to the chronic stage. Such is the case for heart, kidney, liver, and lung where diseases such as diabetes, idiopathic/autoimmune disorders, and nonalcoholic liver disease appear to notably drive the development of fibrosis. Noteworthy is that the severity of these pathologies is characteristically compounded by aging. For these reasons, research groups and drug companies have identified fibrosis as a therapeutic target for which currently, there are essentially no effective options. Although a limited body of published studies are available, most literature indicates that in multiple organs, premenopausal women are protected from developing severe forms of fibrosis suggesting an important role for sex hormones in mitigating this process. Investigators have implemented relevant animal models of organ disease linked to fibrosis supporting in general, these observations. In vitro studies and transgenic animals models have also been used in an attempt to understand the role that sex hormones and related receptors play in the development of fibrosis. However, in the setting of chronic disease in some organs such as the heart older (postmenopausal) women within a few years can quickly approach men in disease severity and develop significant degrees of fibrosis. This review summarizes the current body of relevant literature and highlights the imperative need for a major focus to be placed on understanding the manner in which sex and the presence or absence of related hormones modulates cell phenotypes so as to allow for fibrosis to develop.
器官纤维化的发展受到了越来越多的关注，因为许多发病率不断上升或较高的疾病似乎都进展到了慢性阶段。心脏、肾脏、肝脏和肺部就是这种情况，如糖尿病、特发性/自身免疫性疾病和非酒精性肝病等疾病似乎明显推动了纤维化的发展。值得注意的是，这些病理的严重程度通常会随着年龄的增长而加重。出于这些原因，研究小组和制药公司已经将纤维化确定为一个治疗靶点，而目前基本上没有有效的治疗方法。尽管有一些有限的已发表研究，但大多数文献表明，在多个器官中，绝经前妇女免受严重纤维化形式的影响，这表明性激素在减轻这一过程中起着重要作用。研究人员已经实施了与纤维化相关的器官疾病的相关动物模型，这些观察结果在总体上得到了支持。体外研究和转基因动物模型也被用于试图理解性激素及其相关受体在纤维化发展中的作用。然而，在一些器官（如心脏）的慢性疾病中，几年内老年（绝经后）妇女的疾病严重程度可以迅速接近男性，并发展出显著程度的纤维化。这篇综述总结了目前相关文献的总体情况，并强调迫切需要将重点放在理解性别以及相关激素的存在或缺失如何调节细胞表型上，以便允许纤维化的发展。
