High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes

Abstract

Keratinocytes are essential cells for wound repair. Impaired oral wound healing is common in diabetic patients with periodontal disease. High glucose, or hyperglycemia, impairs the cellular function of different cell types. However, it is unknown whether high glucose has a detrimental effect on the functions of oral keratinocytes. In the current study, a human gingival keratinocyte cell line, telomerase immortalized gingival keratinocytes (TIGK), was treated with high glucose (24 and 48 mM) for up to 120 h. Proliferation, migration, cell viability, and production of markers of differentiation, growth factors and enzymatic antioxidants were assessed after high glucose treatment. The results showed that high glucose significantly inhibited TIGK proliferation and migration. High glucose also induced significant cell death through apoptosis and necrosis as determined by flow cytometry, especially at 120 h after high glucose treatment. Necrosis was the dominant form of cell death induced. Real-time PCR showed that high glucose treatment upregulated mRNA expression of late keratinocyte differentiation makers, such as keratin 1, 10, 13 and loricrin, and downregulated enzymatic antioxidants, including superoxide dismutase 1, catalase, nuclear factor erythroid 2 -related factor 2, heme oxygenase 1. In conclusion, high glucose impairs the proliferation and migration of oral keratinocytes and likely induces cell death through the promotion of late cell differentiation and down-regulation of enzymatic antioxidants.

L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5

“…Previous work has shown that a high-glucose environment impairs the migration and proliferation of cultured skin keratinocytes [35][36][37][38]. Our recent study has also shown that high glucose inhibits oral keratinocyte proliferation and migration, induces late keratinocyte differentiation, and causes cell death [9]. Given the pivotal roles of Arg in cell proliferation, we investigated if and how Arg regulated the proliferation of oral keratinocytes especially under high-glucose conditions.…”

“…Our study here, for the first time, discovered that Arg enhances the proliferation of oral keratinocytes under both low-and high-glucose conditions. Due to the detrimental pathological effects of high glucose on oral keratinocytes [9] and its clinical relevance to diabetes, our studies were performed under high-glucose conditions. RNA sequencing analyses identified CYP1A1 as the top upregulated DEG at both 24 and 48 h after Arg treatment.…”

“…Our recent study demonstrates that high-glucose conditions inhibit oral keratinocyte proliferation and migration [9]. Since keratinocytes are the major cell component in the skin and oral epithelia, with keratinocyte proliferation being critical for re-epithelialization during wound closure [10,11], any strategies that are able to improve keratinocyte proliferation would be beneficial for wound healing, especially in diabetic patients.…”