201. Deletion of theFHL2Gene Attenuating Neovascularization after Corneal Injury
- Author
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Hsueh-Hua Wu, Tzu-Fang Shiu, I-Jong Wang, David Hui-Kang Ma, Ju Chen, Lung-Kun Yeh, Pao-Hsien Chu, Hsin-Chiung Lin, and Shih-Ming Jung
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Blotting, Western ,LIM-Homeodomain Proteins ,Muscle Proteins ,Vascular permeability ,Biology ,Article ,Neovascularization ,Mice ,chemistry.chemical_compound ,Burns, Chemical ,medicine ,Animals ,Sodium Hydroxide ,Corneal Neovascularization ,Homeodomain Proteins ,FHL3 ,medicine.disease ,eye diseases ,Up-Regulation ,FHL2 ,Mice, Inbred C57BL ,Platelet Endothelial Cell Adhesion Molecule-1 ,Vascular endothelial growth factor ,Disease Models, Animal ,Eye Burns ,Vascular endothelial growth factor A ,Gene Expression Regulation ,chemistry ,Cyclooxygenase 2 ,Corneal neovascularization ,Cancer research ,sense organs ,medicine.symptom ,Gene Deletion ,Corneal Injuries ,Transcription Factors - Abstract
The four-and-a-half LIM domain (FHL) protein family is a newly identified group of proteins containing four-and-half LIM domains. This family consists of six members—FHL1, FHL2, FHL3, FHL4, FHL5, and ACT (Activator of CREM in Testis).1–4 The LIM domain is a zinc-binding, cysteine-rich motif consisting of two tandemly repeated zinc fingers that are thought primarily to mediate protein-protein interactions. 1 Johannessen et al.5 showed that human four-and-a-half-LIM-only protein family members, including FHL2, are expressed in a cell- and tissue-specific manner and participate in various cellular processes such as regulation of gene expression, cytoarchitecture, cell adhesion, cell survival, cell mobility, transcription, and signal transduction. Our previous work has demonstrated that FHL2 is abundantly expressed in the vascular system, including blood vessels,3 suggesting that it might play an important physiological or pathologic role in the regulation of the circulatory system.6 Therefore, we have investigated the role of FHL2 protein during corneal angiogenesis induced by chemical and mechanical denudation of corneal and limbal epithelium. Corneal transparency and avascularity are important for maintaining the proper optical performance of the cornea. Corneal neovascularization (CNV) involves the development of new vascular structures in areas that were previously avascular and is a sight-threatening condition associated with cloudy cornea.7 CNV may be induced by infection, inflammation, degeneration, or delayed wound-healing disorders in ocular surfaces. CNV could result from a disrupted balance between the upregulation of angiogenic factors and the downregulation of antiangiogenic factors.7 The extent of CNV was quantified and analyzed in different experimental groups. Vascular endothelial growth factor (VEGF), a key mediator of vasculogenic and angiogenic events, controls pathologic angiogenesis and increased vascular permeability in diseased cornea.7–10 Additionally, the prostaglandin-cyclooxygenase pathway has been reported to influence new blood vessel growth in a variety of tissues. 11–15 The isoenzymes cyclooxygenase (COX)-1 and COX-2 are involved in prostaglandin biosynthesis. Generally, COX-1 is expressed in most tissues and cells, whereas COX-2 is upregulated by cytokines, inflammatory mediators, and tumor progression.16 Overexpression of COX-2 in colon cancer cells and endothelium increases the production of prostaglandins and angiogenic cytokines, migration of endothelial cells, and tube formation.11,16 Therefore, in the present study, the levels of VEGF and COX-2 have been measured in neovascularized cornea and compared among different groups after sodium hydroxide (NaOH) injury. To determine the role of FHL2 in angiogenesis, we assessed the effects of corneal injury in the FHL2-null mice model that we previously generated through homologous recombination.17 Our results suggest that deletion of the FHL2 gene attenuates the process of corneal angiogenesis.
- Published
- 2008
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