NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA.
Molecules. 2023 Oct 10;28(20):7020. doi: 10.3390/molecules28207020.
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 () 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 () and serine- and arginine-rich splicing factor 5 () were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of , , and after L-Arginine treatment. Knockdown of , , and 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 , , and , suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration.
高葡萄糖抑制口腔角质细胞增殖。糖尿病可导致口腔伤口愈合延迟和牙周病。精氨酸是最通用的氨基酸之一，在伤口愈合、器官成熟和发育中发挥重要作用。本研究发现，在高葡萄糖条件下，精氨酸可增强口腔角质细胞增殖。RNA 测序分析发现，在高葡萄糖条件下，经精氨酸处理后，大量基因表达显著上调。细胞色素 P450 家族 1 亚家族 A 成员 1（）在精氨酸处理 24 和 48 小时后上调最显著。基因本体论富集分析发现，细胞增殖和有丝分裂相关的生物学过程，如有丝分裂核分裂、mRNA 加工和细胞周期过程的正调控，显著上调。途径富集分析发现，S 期激酶相关蛋白 2（）和丝氨酸/精氨酸丰富剪接因子 5（）分别是细胞周期和剪接体途径中上调最显著的基因。间接免疫荧光细胞化学证实，经精氨酸处理后，蛋白水平升高。下调、和后，精氨酸对高葡萄糖条件下口腔角质细胞的促增殖作用被消除。总之，精氨酸通过上调、和来增强高葡萄糖条件下口腔角质细胞的增殖，提示口腔护理产品中补充精氨酸可能有益于口腔组织修复和再生。
