L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i>
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...
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MDPI AG
2023-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/20/7020 |
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| author | Junhe Shi Trevor R. Leonardo Chen Han Hiba I. Bangash Dandan Chen Harsh M. Trivedi Lin Chen |
| author_facet | Junhe Shi Trevor R. Leonardo Chen Han Hiba I. Bangash Dandan Chen Harsh M. Trivedi Lin Chen |
| author_sort | Junhe Shi |
| collection | DOAJ |
| 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 (<i>CYP1A1</i>) 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 (<i>SKP2</i>) and serine- and arginine-rich splicing factor 5 (<i>SRSF5</i>) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> after L-Arginine treatment. Knockdown of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> 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 <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i>, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration. |
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| language | English |
| last_indexed | 2024-03-10T21:00:28Z |
| publishDate | 2023-10-01 |
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| series | Molecules |
| spelling | doaj.art-35f0463408244999a51e591ad0a94c1b2023-11-19T17:31:33ZengMDPI AGMolecules1420-30492023-10-012820702010.3390/molecules28207020L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i>Junhe Shi0Trevor R. Leonardo1Chen Han2Hiba I. Bangash3Dandan Chen4Harsh M. Trivedi5Lin Chen6NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, ChinaDepartment 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, USADepartment 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, USAHigh 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 (<i>CYP1A1</i>) 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 (<i>SKP2</i>) and serine- and arginine-rich splicing factor 5 (<i>SRSF5</i>) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> after L-Arginine treatment. Knockdown of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> 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 <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i>, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration.https://www.mdpi.com/1420-3049/28/20/7020L-Argininehigh glucoseoral keratinocyteproliferation<i>CYP1A1</i><i>SKP2</i> |
| spellingShingle | Junhe Shi Trevor R. Leonardo Chen Han Hiba I. Bangash Dandan Chen Harsh M. Trivedi Lin Chen L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> Molecules L-Arginine high glucose oral keratinocyte proliferation <i>CYP1A1</i> <i>SKP2</i> |
| title | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> |
| title_full | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> |
| title_fullStr | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> |
| title_full_unstemmed | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> |
| title_short | L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of <i>CYP1A1</i>, <i>SKP2</i>, and <i>SRSF5</i> |
| title_sort | l arginine enhances oral keratinocyte proliferation under high glucose conditions via upregulation of i cyp1a1 i i skp2 i and i srsf5 i |
| topic | L-Arginine high glucose oral keratinocyte proliferation <i>CYP1A1</i> <i>SKP2</i> |
| url | https://www.mdpi.com/1420-3049/28/20/7020 |
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