Inhibition of LINC00707/miR-223-3p/FKBP5 axis has a protective effect on diabetic kidney disease

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Diabetes Investigation Pub Date : 2025-03-21 DOI:10.1111/jdi.70025

Hongzhen Ye, Yiting Chen, Hong Xia, Lingbo Lv, Lijun Gao

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Abstract

Objective

Research indicates that LINC00707 is abnormally expressed in patients suffering from diabetic kidney disease (DKD). Nevertheless, the precise role of LINC00707 in the context of DKD remains enigmatic and warrants further investigation.

Methods

Initially, RT-qPCR was employed to assess the expression levels of LINC00707 in patients with DKD. Subsequently, we cultured glomerular podocytes under high-glucose conditions. The effects of LINC00707 on cell proliferation, apoptosis, podocyte functionality (Podocin, Nephrin, and CD2AP), oxidative stress (MDA and SOD), and inflammatory responses (IL-1β, IL-6, and TNF-α) were evaluated using CCK-8, flow cytometry, RT-qPCR, and ELISA assays. Finally, we co-regulated LINC00707 alongside its downstream targets to elucidate the molecular mechanisms by which LINC00707 influences podocyte injury.

Results

LINC00707 is abnormally upregulated in DKD patients. Furthermore, a notable inverse correlation has been observed between LINC00707 levels and renal function in these patients. Upon downregulating LINC00707, we observed an increase in cellular proliferative activity, alongside elevated levels of Podocin, Nephrin, and CD2AP. Concurrently, the reduction of LINC00707 was associated with decreased levels of MDA, as well as proinflammatory cytokines. Significantly, the inhibition of miR-223-3p was found to reverse these observed effects. Further investigation revealed that miR-223-3p directly targets FK506-binding protein 5 (FKBP5).

Conclusions

Inhibition of LINC00707 may reduce podocyte damage during hyperglycemia by targeting miR-223-3p/FKBP5.

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抑制LINC00707/miR-223-3p/FKBP5轴对糖尿病肾病具有保护作用。

目的：研究表明，LINC00707在糖尿病肾病（DKD）患者中表达异常。然而，LINC00707在DKD中的确切作用仍然是一个谜，需要进一步的研究。方法：初步采用RT-qPCR方法检测LINC00707在DKD患者中的表达水平。随后，我们在高糖条件下培养肾小球足细胞。通过CCK-8、流式细胞术、RT-qPCR和ELISA检测，评估LINC00707对细胞增殖、凋亡、足细胞功能（Podocin、Nephrin和CD2AP）、氧化应激（MDA和SOD）和炎症反应（IL-1β、IL-6和TNF-α）的影响。最后，我们通过调控LINC00707及其下游靶点来阐明LINC00707影响足细胞损伤的分子机制。结果：LINC00707在DKD患者中表达异常上调。此外，这些患者的LINC00707水平与肾功能之间存在显著的负相关。下调LINC00707后，我们观察到细胞增殖活性增加，同时Podocin、Nephrin和CD2AP水平升高。同时，LINC00707的减少与MDA和促炎细胞因子水平的降低有关。值得注意的是，发现miR-223-3p的抑制可以逆转这些观察到的效应。进一步研究发现miR-223-3p直接靶向fk506结合蛋白5 （FKBP5）。结论：抑制LINC00707可能通过靶向miR-223-3p/FKBP5减轻高血糖期间足细胞损伤。

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来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).