Abstract
BackgroundDiabetic nephropathy (DN) is the most common causes of end-stage renal disease. Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is connected with the development of DN, but the role of CDKN2B-AS1 in DN has not been entirely elucidated.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure CDKN2B-AS1 and miR-98-5p levels. Cell viability, proliferation, and apoptosis were analyzed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or flow cytometry assays. Protein levels were measured by western blotting. The relationship between CDKN2B-AS1 or notch homolog 2 (NOTCH2) and miR-98-5p was verified via dual-luciferase reporter assay.ResultsCDKN2B-AS1 and NOTCH2 were upregulated in the serum of DN patients and high glucose-disposed human podocytes (HPCs) and human renal tubular cells (HK-2), whereas miR-98-5p was downregulated. High glucose repressed viability and accelerated apoptosis of HPCs and HK-2 cells. CDKN2B-AS1 knockdown impaired high glucose-induced apoptosis and fibrosis of HPCs and HK-2 cells. Mechanistically, CDKN2B-AS1 sponged miR-98-5p to regulate NOTCH2 expression. Also, CDKN2B-AS1 inhibition-mediated effects on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells were weakened by miR-98-5p inhibitor. Also, NOTCH2 knockdown partly reversed miR-98-5p inhibitor-mediated impacts on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells.ConclusionHigh glucose-induced CDKN2B-AS1 promoted apoptosis and fibrosis via the TGF-β1 signaling mediated by the miR-98-5p/NOTCH2 axis in HPCs and HK-2 cells.
Highlights
Diabetic nephropathy (DN), a progressive kidney disease caused by diabetes, is characterized by persistent albuminuria and a gradual decline in estimated glomerular filtration rate [1, 2]
CDKN2B-AS1 was upregulated in DN and high glucose-induced human podocytes (HPCs) and HK-2 cells
We found that CDKN2B-AS1 induced apoptosis and fibrosis through upregulating notch homolog 2 (NOTCH2) via sponging miR-98-5p under high glucose treatment
Summary
Diabetic nephropathy (DN), a progressive kidney disease caused by diabetes, is characterized by persistent albuminuria and a gradual decline in estimated glomerular filtration rate [1, 2]. LncRNA GAS5 decreased pyroptosis and oxidative stress via sponging miR-452-5p in high glucose-induced renal tubular cells [11]. Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is connected with the development of diabetes [12], coronary heart disease [13], atherosclerosis [14], and cancers [15]. MiR-98-5p mediated renal fibrosis and epithelial-to-mesenchymal in DN [19]. It is unclear whether CDKN2B-AS1 mediates the development of DN via miR-98-5p. Diabetic nephropathy (DN) is the most common causes of end-stage renal disease. Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is connected with the development of DN, but the role of CDKN2B-AS1 in DN has not been entirely elucidated
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