Silencing LncRNA SNHG14 alleviates renal tubular injury via the miR-483-5p/HDAC4 axis in diabetic kidney disease.

Autor: Huang Q; Department of Nephrology, Gongan Hospital of Traditional Chinese Medicine, Hubei, 434300, China., Qiu T; Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, 201800, China., Chen H; School of Medicine, Tongji University, No.500, Zhennan Road, Taopu Town, Shanghai, 200092, China. Chenhuanzhen0626@163.com.; Department of Endocrinology and Metabolism, Shanghai Jiangong Hospital, No.666 Zhongshan North Road, Hongkou District, Shanghai, 200083, China. Chenhuanzhen0626@163.com., Tian T; Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China., Wang D; Department of Endocrinology and Metabolism, Shanghai Jiangong Hospital, No.666 Zhongshan North Road, Hongkou District, Shanghai, 200083, China., Lu C; Endocrinology Department, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiang West Road, Yuexiu District, Guangzhou, Guangdong, 510120, China. 351939278@qq.com.
Jazyk: angličtina
Zdroj: Hormones (Athens, Greece) [Hormones (Athens)] 2024 Oct 08. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1007/s42000-024-00606-2
Abstrakt: Purpose: This study explored the clinical value of long non-coding RNA small nucleolar RNA host gene 14 (SNHG14) in diabetic kidney disease (DKD) and the mechanism of renal tubular injury.
Methods: Patients with DKD, type 2 diabetes mellitus (T2DM) and healthy individuals (HVs) were included, as well as the human proximal tubular epithelial cell line (HK-2) induced by high glucose was also included. The mRNA levels of SNHG14 in the serum and cells were detected using RT-qPCR. Diagnostic significance was examined using receiver operating characteristic (ROC) analysis. A commercial test kit, flow cytometry, and enzyme-linked immunosorbent assays were employed to assess reactive oxygen species (ROS) production, apoptosis, inflammatory factor secretion, and extracellular matrix protein levels in HK-2 cells. The dual-luciferase reporter assay and RNA immunoprecipitation were used to validate miR-483-5p concerning SNHG14 or histone deacetylase 4 (HDAC4).
Results: SNHG14 and HDAC4 levels were elevated in the serum of DKD patients and HG-induced HK-2 cells, while miR-483-5p levels were decreased (P < 0.001). SNHG14 increased HDAC4 levels by sponging miR-483-5p. Elevated SNHG14 levels significantly differentiated DKD patients from HVs (AUC = 0.944) and T2DM (AUC = 0.867). Silencing of SNHG14 alleviated HG-induced ROS production and apoptosis as well as the over-secretion of inflammatory factors and extracellular matrix proteins; however, this alleviation was typically suppressed by low expression of miR-483-5p (P < 0.001). Elevated miR-483-5p alleviates HG-induced renal tubular injury, but this alleviation is suppressed by HDAC4 overexpression.
Conclusion: In summary, suppression of SNHG14 has been shown in our study to mitigate renal tubular injury in DKD by regulating apoptosis, oxidative stress, inflammation, and fibrosis through the miR-483-5p/HDAC4 axis.
(© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)
Databáze: MEDLINE
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