Functional study of Krt17 in corneal epithelial regeneration and stemness regulation.

Abstract

Corneal limbal epithelial stem cells (LSCs) are essential for maintaining corneal epithelial homeostasis and mediating injury repair. Although various LSC-associated markers have been reported, the dynamic expression characteristics of the stress-inducible keratin 17 (Krt17) during corneal development and injury, as well as its potential association with LSC function, remain insufficiently explored. In this study, we systematically evaluated the temporal expression pattern of Krt17 in mouse corneal development and wound healing, and further validated its functional relevance to stemness, proliferation, and differentiation in primary mouse corneal epithelial cells and murine corneal epithelial stem/progenitor cell line (TKE2). The results showed that Krt17 was broadly distributed in the basal layer of the corneal epithelium during early postnatal stages and later became progressively restricted to the limbal region, exhibiting a region-specific expression pattern highly consistent with stemness and proliferation markers such as Krt14, Krt15, p63, and Ki67. In corneal injury models, Krt17 was rapidly upregulated after damage, peaked during the early phase of repair, and then declined to baseline levels upon completion of re-epithelialization. Functional assays in vitro further revealed that Krt17 overexpression enhanced clonal formation ability of primary corneal epithelial cells and promoted the migratory capacity of TKE2 cells, while helping to maintain an undifferentiated state and proliferative potential under differentiation stimuli. Conversely, Krt17 knockdown markedly impaired these functions. Collectively, these findings suggest that Krt17 is not only associated with corneal epithelial stemness but may also contribute to maintaining corneal epithelial homeostasis and regeneration by regulating a less differentiated and proliferative state.