Omoto Masahiro, Suri Kunal, Amouzegar Afsaneh, Li Mingshun, Katikireddy Kishore R, Mittal Sharad K, Chauhan Sunil K
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
Mol Ther. 2017 Aug 2;25(8):1881-1888. doi: 10.1016/j.ymthe.2017.04.020. Epub 2017 May 11.
Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.
角膜损伤是导致眼部发病和视力损害的主要原因之一。最佳的上皮伤口愈合对于损伤后角膜的完整性和透明度至关重要。肝细胞生长因子(HGF)是一种主要调节上皮细胞功能的促有丝分裂剂和运动因子。在此,我们研究了HGF在体外和体内炎症条件下对角膜上皮细胞(CECs)增殖的影响。我们证明,HGF不仅在稳态条件下促进CECs增殖,还能逆转炎症环境对这些细胞的抗增殖作用。此外,利用眼部损伤小鼠模型,我们表明HGF治疗可抑制眼部炎症并积极增强CECs增殖,从而改善并加速角膜上皮修复。这些发现具有潜在的转化意义,并可为开发基于HGF的新型角膜上皮缺损治疗方法提供框架。