Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye

Abstract

Glucocorticoids play diverse roles in almost all physiological systems of the body, including both anti-inflammatory and immunosuppressive roles. Synthetic glucocorticoids are one of the most widely prescribed drugs and are used in the treatment of conditions such as autoimmune diseases, allergies, ocular disorders and certain types of cancers. In the interest of investigating glucocorticoid actions in the cornea of the eye, we established that multiple cell types in mouse corneas express functional glucocorticoid receptor (GR) with corneal epithelial cells having robust expression. To define glucocorticoid actions in a cell type-specific manner, we employed immortalized human corneal epithelial (HCE) cell line to define the glucocorticoid transcriptome and elucidated its functions in corneal epithelial cells. Over 4000 genes were significantly regulated within 6 hours of dexamethasone treatment, and genes associated with cell movement, cytoskeletal remodeling and permeability were highly regulated. Real-time in vitro wound healing assays revealed that glucocorticoids delay wound healing by attenuating cell migration. These functional alterations were associated with cytoskeletal remodeling at the wounded edge of a scratch-wounded monolayer. However, glucocorticoid treatment improved the organization of tight-junction proteins and enhanced the epithelial barrier function. Our results demonstrate that glucocorticoids profoundly alter corneal epithelial gene expression and many of these changes likely impact both wound healing and epithelial cell barrier function.

Endoplasmic Reticulum Stress PERK-ATF4-CHOP Pathway Is Associated with Hypothalamic Neuronal Injury in Different Durations of Stress in Rats

“…The present study demonstrated that prolonged stress exposure resulted in significantly increased serum glucocorticoid levels, suggesting an increased defense capability to external stimuli by regulating the HPA axis and ultimately maintaining homeostasis. Numerous studies have indicated that glucocorticoids play a critical role in maintaining cardiovascular stability, stabilizing lysosomal membranes, anti-inflammation, anti-shock mechanisms, and reducing bacterial endotoxin damage (Kasahara et al, 2015; Kadmiel et al, 2016). However, by increasing the stress period to 21 days, serum glucocorticoid levels significantly decreased compared with stress exposure of 14 days.…”

Crosstalk between Aryl Hydrocarbon Receptor and Glucocorticoid Receptor in Human Retinal Pigment Epithelial Cells

“…As such, glucocorticoid receptor (GR), a stress transcription factor, has shown to play a role in RPE physiology and AMD progression. Activation of GR by Dex-induced proliferation of cultured retinal pigment epithelial cells [33] and loss of GR in the retina result in the thinning of the inner nuclear layer of the peripheral retina in adult mice [34]. Because AHR and GR are closely related in AMD progression, we attempted to study AHR and GR crosstalk in ARPE-19 cells.…”

Fluorometholone modulates gene expression of ocular surface mucins

“…; Kadmiel et al. ). Fluorometholone is a fluorinated corticosteroid that has been shown to be efficacious in relieving the symptoms of dry eye in non‐Sjogren and Sjogren's patients (Jee et al.…”