Falero-Perez Juliana, Song Yong-Seok, Sorenson Christine M, Sheibani Nader
Departments of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine, Madison, WI USA.
Departments of Pediatrics, University of Wisconsin School of Medicine, Madison, WI USA.
Trends Cell Mol Biol. 2018;13:27-45.
CYP1B1 is a member of the CYP1 subfamily of CYP superfamily of enzymes, which contains three members, CYP1A1, CYP1A2, and CYP1B1. CYP1B1 is expressed in both adult and fetal human extrahepatic tissues, including the parenchymal and stromal cells of most organs. Mutations in the CYP1B1 gene are linked to the development of primary congenital glaucoma in humans. However, the underlying mechanisms remain unknown. Using -deficient mice, we showed that CYP1B1 is constitutively expressed in retinal vascular cells with a significant role in retinal neovascularization during oxygen-induced ischemic retinopathy. We also showed CYP1B1 is constitutively expressed in trabecular meshwork (TM) cells and its expression plays a significant role in the normal development and function of the TM tissue. We have observed that germline deletion of is associated with increased oxidative stress in the retinal vascular and TM cells in culture, and retinal and TM tissue in vivo. We showed increased oxidative stress was responsible for altered production of the extracellular matrix proteins and had a significant impact on cellular integrity and function of these tissues. Collectively, our studies have established an important role for CYP1B1 expression in modulation of tissue integrity and function through the regulation of cellular redox homeostasis and extracellular microenvironment.
细胞色素P450 1B1（CYP1B1）是细胞色素P450超家族1亚家族的成员，该亚家族包含三个成员，即细胞色素P450 1A1（CYP1A1）、细胞色素P450 1A2（CYP1A2）和细胞色素P450 1B1（CYP1B1）。CYP1B1在成人和胎儿的肝外组织中均有表达，包括大多数器官的实质细胞和基质细胞。CYP1B1基因的突变与人类原发性先天性青光眼的发生有关。然而，其潜在机制仍不清楚。利用基因敲除小鼠，我们发现CYP1B1在视网膜血管细胞中持续表达，在氧诱导的缺血性视网膜病变期间的视网膜新生血管形成中起重要作用。我们还发现CYP1B1在小梁网（TM）细胞中持续表达，其表达在TM组织的正常发育和功能中起重要作用。我们观察到，基因敲除与培养的视网膜血管和TM细胞以及体内视网膜和TM组织中的氧化应激增加有关。我们发现氧化应激增加导致细胞外基质蛋白产生改变，并对这些组织的细胞完整性和功能产生重大影响。总的来说，我们的研究确立了CYP1B1表达在通过调节细胞氧化还原稳态和细胞外微环境来调节组织完整性和功能方面的重要作用。
