High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes

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...

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Main Authors: Junhe Shi, Chen Han, Dandan Chen, Harsh M. Trivedi, Hiba I. Bangash, Lin Chen
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/44/9/275
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author Junhe Shi
Chen Han
Dandan Chen
Harsh M. Trivedi
Hiba I. Bangash
Lin Chen
author_facet Junhe Shi
Chen Han
Dandan Chen
Harsh M. Trivedi
Hiba I. Bangash
Lin Chen
author_sort Junhe Shi
collection DOAJ
description 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.
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spelling doaj.art-b8149c5e2b994a22b67ffdb5007d41d42023-11-23T15:39:09ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-09-014494015402710.3390/cimb44090275High Glucose Induces Late Differentiation and Death of Human Oral KeratinocytesJunhe Shi0Chen Han1Dandan Chen2Harsh M. Trivedi3Hiba I. Bangash4Lin Chen5Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, ChinaDepartment of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USAColgate-Palmolive Company, Piscataway, NJ 08854, USAColgate-Palmolive Company, Piscataway, NJ 08854, USADepartment of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USAKeratinocytes 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.https://www.mdpi.com/1467-3045/44/9/275high glucosegingivakeratinocytedifferentiationapoptosisnecrosis
spellingShingle Junhe Shi
Chen Han
Dandan Chen
Harsh M. Trivedi
Hiba I. Bangash
Lin Chen
High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
Current Issues in Molecular Biology
high glucose
gingiva
keratinocyte
differentiation
apoptosis
necrosis
title High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
title_full High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
title_fullStr High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
title_full_unstemmed High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
title_short High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
title_sort high glucose induces late differentiation and death of human oral keratinocytes
topic high glucose
gingiva
keratinocyte
differentiation
apoptosis
necrosis
url https://www.mdpi.com/1467-3045/44/9/275
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