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L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5
High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhan...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609441/ https://www.ncbi.nlm.nih.gov/pubmed/37894498 http://dx.doi.org/10.3390/molecules28207020 |
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author | Shi, Junhe Leonardo, Trevor R. Han, Chen Bangash, Hiba I. Chen, Dandan Trivedi, Harsh M. Chen, Lin |
author_facet | Shi, Junhe Leonardo, Trevor R. Han, Chen Bangash, Hiba I. Chen, Dandan Trivedi, Harsh M. Chen, Lin |
author_sort | Shi, Junhe |
collection | PubMed |
description | High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhance oral keratinocyte proliferation under high-glucose conditions. RNA sequencing analysis discovered a significant number of genes differentially upregulated following L-Arginine treatment under high-glucose conditions. Cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was the most significantly upregulated gene at 24 and 48 h after L-Arginine treatment. Gene Ontology enrichment analysis found that cell proliferation- and mitosis-related biological processes, such as mitotic nuclear division, mRNA processing, and positive regulation of cell cycle processes, were significantly upregulated. Pathway enrichment analysis found that S-phase kinase-associated protein 2 (SKP2) and serine- and arginine-rich splicing factor 5 (SRSF5) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of CYP1A1, SKP2, and SRSF5 after L-Arginine treatment. Knockdown of CYP1A1, SKP2, and SRSF5 abolished the enhanced proliferative effect of L-Arginine on oral keratinocytes under high-glucose conditions. In conclusion, L-Arginine enhances oral keratinocyte proliferation under high-glucose conditions via upregulation of CYP1A1, SKP2, and SRSF5, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration. |
format | Online Article Text |
id | pubmed-10609441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106094412023-10-28 L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 Shi, Junhe Leonardo, Trevor R. Han, Chen Bangash, Hiba I. Chen, Dandan Trivedi, Harsh M. Chen, Lin Molecules Article High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhance oral keratinocyte proliferation under high-glucose conditions. RNA sequencing analysis discovered a significant number of genes differentially upregulated following L-Arginine treatment under high-glucose conditions. Cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was the most significantly upregulated gene at 24 and 48 h after L-Arginine treatment. Gene Ontology enrichment analysis found that cell proliferation- and mitosis-related biological processes, such as mitotic nuclear division, mRNA processing, and positive regulation of cell cycle processes, were significantly upregulated. Pathway enrichment analysis found that S-phase kinase-associated protein 2 (SKP2) and serine- and arginine-rich splicing factor 5 (SRSF5) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of CYP1A1, SKP2, and SRSF5 after L-Arginine treatment. Knockdown of CYP1A1, SKP2, and SRSF5 abolished the enhanced proliferative effect of L-Arginine on oral keratinocytes under high-glucose conditions. In conclusion, L-Arginine enhances oral keratinocyte proliferation under high-glucose conditions via upregulation of CYP1A1, SKP2, and SRSF5, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration. MDPI 2023-10-10 /pmc/articles/PMC10609441/ /pubmed/37894498 http://dx.doi.org/10.3390/molecules28207020 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shi, Junhe Leonardo, Trevor R. Han, Chen Bangash, Hiba I. Chen, Dandan Trivedi, Harsh M. Chen, Lin L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title_full | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title_fullStr | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title_full_unstemmed | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title_short | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5 |
title_sort | l-arginine enhances oral keratinocyte proliferation under high-glucose conditions via upregulation of cyp1a1, skp2, and srsf5 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609441/ https://www.ncbi.nlm.nih.gov/pubmed/37894498 http://dx.doi.org/10.3390/molecules28207020 |
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