Intracellular glucose starvation affects gingival homeostasis and autophagy.

Intracellular glucose starvation affects gingival homeostasis and autophagy.
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DOI:
10.1038/s41598-022-05398-2
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发表时间:
2022-01-24
期刊:
影响因子:
4.6
通讯作者:
Umeda M
Umeda M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li R;Kato H;Taguchi Y;Umeda M

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人牙龈成纤维细胞(HGnFs)通过活跃的增殖和迁移维持牙周组织的稳态。临床上认为,即使在牙周手术后不久营养物(例如葡萄糖)供应不足的环境中,牙龈组织的伤口愈合能力也得以维持。然而,这种葡萄糖缺乏环境对HGnFs的影响仍不清楚。本研究旨在探讨低糖环境对促性腺激素释放因子稳态的影响。我们评估牙龈伤口愈合检查细胞增殖和迁移和胶原蛋白的合成,在100,50,25,和0毫克/分升的葡萄糖在体外培养的HGnFs。通过测定乳酸脱氢酶(LDH)和活性氧(ROS)水平来确定细胞应激水平。通过测定葡萄糖转运蛋白1(GLUT 1)mRNA表达、葡萄糖摄取试验、乳酸和ATP产生来研究低葡萄糖浓度下HGnFs的葡萄糖代谢。研究了分子效应,重点是LKB 1-AMPK信号通路。通过测量自噬相关蛋白的水平来评估葡萄糖剥夺的HGnFs中的自噬活性。低葡萄糖水平增加细胞应激水平、自噬活性,并通过LKB 1-AMPK信号通路增强葡萄糖代谢,提供更多ATP以促进伤口愈合。我们关于葡萄糖转移的研究结果表明牙龈伤口的快速愈合。
Human gingival fibroblasts (HGnFs) maintain periodontal tissue homeostasis through active proliferation and migration. Clinically, it is considered that the wound-healing ability of the gingival tissue is maintained even in environments with insufficient supply of nutrients, such as glucose, immediately after periodontal surgery. However, the effects of such glucose-deficient environments on HGnFs remain unclear. This study aimed to investigate the effects of low-glucose environment on HGnFs homeostasis. We evaluated gingival wound healing by examining cell proliferation and migration and collagen synthesis in HGnFs cultured in 100, 50, 25, and 0 mg/dL glucose in vitro. The cellular stress levels were determined by measuring the lactate dehydrogenase (LDH) and reactive oxygen species (ROS) levels. The glucose metabolism of HGnFs in the low-glucose concentrations was studied by measuring glucose transporter type 1 (GLUT1) mRNA expression, glucose uptake assays, lactate and ATP productions. Molecular effects were examined with a focus on the LKB1-AMPK signaling pathway. Autophagy activity in glucose-deprived HGnFs was evaluated by measuring the levels of autophagy-related proteins. Low glucose levels increased cellular stress levels, autophagy activity, and enhanced glucose metabolism through the LKB1-AMPK signaling pathway, providing more ATPs to promote wound healing. Our results regarding glucose transfer suggest the rapid healing of gingival wounds.
DOI: 10.1083/jcb.152.4.657
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