Chan Kenrick Kai-Yuen, Lee Alan Chun-Kit, Chung Shing-Yan Roy, Wong Man-Sau, Do Chi-Wai, Lam Thomas Chuen, Kong Hang-Kin
Centre for Eye and Vision Research, 17W Hong Kong Science Park, Taipo, Hong Kong SAR 999077, China.
Department of Applied Biology and Chemical Technology, Faculty of Science, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, China.
J Proteome Res. 2025 Jun 6;24(6):2771-2782. doi: 10.1021/acs.jproteome.4c01046. Epub 2025 May 13.
Dry eye syndrome (DES) affects millions of people worldwide. However, as the cellular responses of the corneal epithelium under hyperosmotic stress remain unclear, this study investigated the proteomic changes between human corneal epithelial cells (HCECs) cultured with isosmotic and hyperosmotic media. Under hyperosmotic stress, HCECs increased expressions of sodium-coupled neutral amino acid transporter (SNAT2), glutaminase (GLS-1), and a few isoforms of heat shock protein and aldo-keto reductase family 1. The expressions of SNAT2 and GLS-1 were increased after 6 h of exposure to hyperosmotic stress but not by glutamine deprivation. The hyperosmotic stress increased intracellular levels of glutamine, mitochondrial superoxide, and mitochondrial membrane potential and induced mitochondrial fission in HCECs. Thus, the intracellular level of glutamine was elevated in the hyperosmotic stressed HCECs via the upregulation of SNAT2. Glutamine can act as an osmolyte to regulate the osmolarity of HCECs or be converted to glutamate by GLS-1 for the tricarboxylic acid cycle and oxidative phosphorylation to maintain ATP production under the hyperosmotic stress-induced mitochondrial fission. Thus, the increases in the expressions of SNAT2 and GLS-1 are key osmoregulations in HCECs upon the hyperosmotic stress and may act as corneal biomarkers for monitoring DES progression.
干眼症（DES）影响着全球数百万人。然而，由于高渗应激下角膜上皮细胞的细胞反应仍不清楚，本研究调查了在等渗和高渗培养基中培养的人角膜上皮细胞（HCECs）之间的蛋白质组学变化。在高渗应激下，HCECs增加了钠偶联中性氨基酸转运体（SNAT2）、谷氨酰胺酶（GLS-1）以及一些热休克蛋白和醛糖还原酶家族1同工型的表达。暴露于高渗应激6小时后，SNAT2和GLS-1的表达增加，但谷氨酰胺缺乏并未导致这种增加。高渗应激增加了HCECs中谷氨酰胺的细胞内水平、线粒体超氧化物和线粒体膜电位，并诱导了线粒体分裂。因此，通过上调SNAT2，高渗应激下的HCECs中谷氨酰胺的细胞内水平升高。谷氨酰胺可以作为一种渗透剂来调节HCECs的渗透压，或者被GLS-1转化为谷氨酸用于三羧酸循环和氧化磷酸化，以在高渗应激诱导的线粒体分裂下维持ATP的产生。因此，SNAT2和GLS-1表达的增加是高渗应激下HCECs中的关键渗透调节，可能作为监测DES进展的角膜生物标志物。
