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Background: Diabetic nephropathy (DN) is a serious microvascular complication of diabetes that may lead to chronic renal failure and end-stage renal disease. Circular RNAs (circRNAs) play important roles in DN progression. However, the action of circRNA ADP ribosylation factor 3 (circ_Arf3) in high glucose (HG)-induced change is still unclear.
Methods: Mouse mesangial cells (MCs) were treated with 30 mM HG as a DN cell model in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression levels of circ_Arf3, microRNA (miR)-452-5p and muscleblind like splicing regulator 1 (Mbnl1). The proliferation of HG-treated MCs was assessed using 5 Ethynyl 2' deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assays, and the levels of proliferation and fibrosis-related proteins and Mbnl1 were detected by Western blot. Dual-luciferase reporter and RNA pull-down assays were utilized to determine the relationship between miR-452-5p and circ_Arf3 or Mbnl1.
Results: Our results discovered that circ_Arf3 and Mbnl1 were lowly expressed in HG-treated MCs, while miR-452-5p expression was up-regulated. Moreover, circ_Arf3 was mainly located in the cytoplasm and had a ring-like stable structure. Functional assays demonstrated that overexpression of circ_Arf3 prevented cell proliferation and fibrous formation in HG-treated MCs. Circ_Arf3 could sponge miR-452-5p, and the effect of circ_Arf3 overexpression was reversed by enhanced expression of miR-452-5p. Mbnl1 was a direct target of miR-452-5p. Knockdown of Mbnl1 abolished the suppressive effects of miR-452-5p inhibitor on proliferation and fibrosis-related protein expression in HG-treated MCs. Moreover, circ_Arf3 regulated Mbnl1 through miR-452-5p.
Conclusion: Overexpression of circ_Arf3 prevents cell proliferation and fibrous formation in HG-treated MCs by regulating the expression of Mbnl1 via miR-452-5p.
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http://dx.doi.org/10.2147/DMSO.S400530 | DOI Listing |
Ren Fail
December 2025
Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China.
To investigate the clinical significance and role of miRNAs with shared patterns in both peripheral blood and kidney tissue-derived extracellular vesicles (EVs) in diabetic kidney disease (DKD). miRNA-Seq was performed on plasma EV samples from DKD and diabetes mellitus (DM) patients, and the validation, clinical significance and mechanistic exploration of the specific differentially expressed miRNAs (De-miRNAs) were evaluated in a cohort of DKD-derived plasma and glomerular mesangial biopsies and high glucose (HG)-treated mesangial cells (MCs). A total of 15 EV-derived De-miRNAs was identified by miRNA-Seq, among which miR-3147 was the most significantly differentially expressed.
View Article and Find Full Text PDFRen Fail
December 2025
Department of Diabetes Nephrology, Zhangzhou Hospital of Traditional Chinese Medicine, Zhangzhou, China.
Diabetic nephropathy (DN) is a serious microvascular complication of diabetes and the main cause of end-stage renal disease. Smurf2 is a member of ubiquitin ligases. In this study, we aimed to investigate the mechanism by which Smurf2 mediated the development of DN.
View Article and Find Full Text PDFTissue Cell
August 2025
The Department of Nephrology, the First People's Hospital of Sihong County, Suqian, Jiangsu, China. Electronic address:
Background: Diabetic nephropathy (DN) poses a significant global health burden due to its progressive nature leading to end-stage renal disease and increased mortality rates. Here, we explored the effects of Tripartite Motif Containing 33 (Trim33) on cell viability and fibrosis of mesangial cells (MCs).
Methods: MCs were treated with 30 mM D-glucose (HG) and mice were injected with 50 mg/kg STZ to establish the DN model.
Acta Pharmacol Sin
July 2025
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China.
Mesangial cells (MCs) are the most active intrinsic cells in the glomerulus. MCs excessively proliferate at the early stage of diabetic kidney disease (DKD), eventually causing glomerular sclerosis and even renal failure; inhibiting glomerular MC proliferation in early DKD is a promising prevention and treatment strategy for early DKD. Our previous study shows that Yin Yang 1 (YY1), a zinc finger protein, is a novel regulator of DKD-induced renal fibrosis.
View Article and Find Full Text PDFJ Diabetes
June 2024
Department of Renal Medicine, Huai'an Rehabilitation Hospital (Jinhu People's Hospital), Huai'an, China.
Background: Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored.
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