ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway.

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Open Medicine Pub Date : 2024-10-10 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-1037
Ying Wang, Jiang Chang, Fa Wang, Lianying Lai, ShiXu Yang, Yueying Fu, Xingtian Ma, Chuan Yun
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Abstract

Background: Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, holds a role in cancer, inflammation, and immunity. However, its specific function in the nephropathy and high-glucose-induced human renal tubular epithelial cells (HK-2) injury in diabetic db/db mice is not clear.

Methods: This study explored the expression characteristics of ADAR1 in proximal renal tubular cells of diabetic db/db mice, examining its function in the mechanism of high-glucose-induced HK-2 cell injury. Furthermore, it elucidated the molecular mechanism underlying the protective effect of ADAR1, the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mammalian target of the rapamycin (mTOR) signaling. We observed a decrease in ADAR1 expression in proximal tubular cells of diabetic db/db mice, accompanied by an increase in the expression of inflammation-related markers (PI3K/AKT/mTOR).

Results: We constructed and validated ADAR1-overexpression plasmids and used an ADAR1 inhibitor (8-azaadenosine) to carry out cell experiments. The upregulation of ADAR1 expression alleviated high-glucose-induced endoplasmic reticulum stress, reduced HK-2 cell apoptosis, and reduced the expression of inflammation-related indicators (PI3K/AKT/mTOR).

Conclusion: Taken together, the pivotal roles of ADAR1 in the progression of proximal renal tubulopathy and the mechanism of high-glucose-induced HK-2 injury in diabetic db/db mice suggest that ADAR1 may be a potential key factor in slowing the progression of diabetic kidney disease.

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ADAR1 通过抑制 PI3K/AKT/mTOR 信号通路,在高糖条件下对近端肾小管细胞起到保护作用。
背景:作用于 RNA 的腺苷脱氨酶 1(ADAR1)是一种 RNA 编辑酶,在癌症、炎症和免疫中发挥作用。然而,它在糖尿病 db/db 小鼠肾病和高血糖诱导的人肾小管上皮细胞(HK-2)损伤中的具体功能尚不清楚:本研究探讨了 ADAR1 在糖尿病 db/db 小鼠近端肾小管细胞中的表达特征,研究了其在高血糖诱导 HK-2 细胞损伤机制中的功能。此外,研究还阐明了ADAR1保护作用的分子机制--调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/Akt)/雷帕霉素靶标(mTOR)信号转导。我们观察到糖尿病 db/db 小鼠近端肾小管细胞中 ADAR1 的表达减少,同时炎症相关标志物(PI3K/AKT/mTOR)的表达增加:我们构建并验证了 ADAR1 外表达质粒,并使用 ADAR1 抑制剂(8-氮杂腺苷)进行了细胞实验。ADAR1表达的上调缓解了高葡萄糖诱导的内质网应激,减少了HK-2细胞的凋亡,并降低了炎症相关指标(PI3K/AKT/mTOR)的表达:综上所述,ADAR1 在糖尿病 db/db 小鼠近端肾小管病变进展中的关键作用以及高糖诱导 HK-2 损伤的机制表明,ADAR1 可能是减缓糖尿病肾病进展的潜在关键因素。
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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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