High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Shen, Hua; Fang, Kai; Guo, Haifeng; Wang, Guojun

doi:10.1248/bpb.b18-00951

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…One report claimed that miR-15b-5p could reduce HG-induced podocyte injury by repressing inflammation response, oxidative stress, and apoptosis of podocyte via downregulating Sema3A [22]. Shen et al revealed that miR-15b-5p overexpression could reduce apoptosis in human kidney cells induced by HG [23]. Herein, CDKN2B-AS1 was proved as a sponge for miR-15b-5p in HMCs.…”

Section: Discussionmentioning

confidence: 99%

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Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis

Chang

Fang

et al. 2020

Diabetol Metab Syndr

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Background Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been reported to be related to diabetic nephropathy (DN) progression. However, the regulatory mechanisms of CDKN2B-AS1 in DN are unclear. Methods High glucose (HG) was used to induce human mesangial cells (HMCs) for establishing the DN model. Expression levels of CDKN2B-AS1, microRNA (miR)-15b-5p, wingless-Type family member 2B (WNT2B) mRNA in serum and HMCs were detected through quantitative real-time polymerase chain reaction (qRT-PCR). The viability and cell cycle progression of HMCs were determined with Cell Counting Kit-8 (CCK-8) or flow cytometry assays. The levels of several proteins and inflammatory factors in HMCs were analyzed by western blotting or enzyme-linked immunosorbent assay (ELISA). The relationship between CDKN2B-AS1 or WNT2B and miR-15b-5p was verified with dual-luciferase reporter assay. Results CDKN2B-AS1 and WNT2B were upregulated while miR-15b-5p was downregulated in serum of DN patients and HG-treated HMCs. CDKN2B-AS1 inhibition reduced HG-induced viability, cell cycle progression, ECM accumulation, and inflammation response in HMCs. CDKN2B-AS1 regulated WNT2B expression via competitively binding to miR-15b-5p. MiR-15b-5p inhibitor reversed CDKN2B-AS1 knockdown-mediated influence on viability, cell cycle progression, ECM accumulation, and inflammation response of HG-treated HMCs. The repressive effect of miR-15b-5p mimic on viability, cell cycle progression, ECM accumulation, and inflammation response of HG-treated HMCs was abolished by WNT2B overexpression. Conclusion CDKN2B-AS1 regulated HG-induced HMC viability, cell cycle progression, ECM accumulation, and inflammation response via regulating the miR-15b-5p/WNT2B axis, provided a new mechanism for understanding the development of DN.

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Section: Discussionmentioning

confidence: 99%

“…MiR-34a could contribute to renal fibrosis through decreasing klotho expression in HK-2 cells [21]. It was reported that miR-15b-5p exerted a protective role in DN [22,23]. As far as we know, the targeting relationship between CDKN2B-AS1 and miR-15b-5p in DN is unclear.…”

Section: Introductionmentioning

confidence: 98%

Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis

Chang

Fang

et al. 2020

Diabetol Metab Syndr

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“…The etiology of DN has not been fully elucidated, and it is believed that the release of many cytokines and reactive oxygen species from MC cells were induced by high glucose resulting from disorders of glucolipid metabolism, which subsequently causes oxidative stress, rheological changes and inflammatory responses in glomeruli, resulting in cell proliferation and division, leading to the Trop J Pharm Res, September 2021; 20 (9): 1824 aggregation of extracellular matrix in MC cells and reducing renal function [12]. NF-κB is an important nuclear transcription factor in the nucleus that regulates the activation and expression of many genes, and participates in the signal transmission of cellular inflammatory response [13]. It was discovered that NF-κB was involved in the process of renal injury in DN via induction of inflammatory response and production of vascular endothelial growth factor [14].…”

Section: Discussionmentioning

confidence: 99%

Effects of Qijin granules on high glucose-induced proliferation, apoptosis and expression of nuclear factor- κB and MCP-1 in rat glomerular mesangial cells

Yang¹,

Xiong²,

Yang³

et al. 2021

Trop. J. Pharm Res

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Purpose: To investigate the effects of Qijin granules on high glucose-induced proliferation and apoptosis in rat glomerular mesangial cells (MC).Methods: MC cells from rats were passaged and cultured, and randomly divided into control group (CNG), high glucose group (HGG), Western medicine group (WMG, high glucose + Benazepril + Gliquidone), and Qijin granules 1/2/3 group (high glucose + different doses of Qijin granules). Mesangial cells proliferation was measured using MTT assay. The NF-κB, MCP-1 and inflammatory factors in supernatant were determined by ELISA. Apoptosis rate and cell cycle were assessed by flow cytometry. The apoptosis-related TGF-β1/Smad signaling pathway-related protein expressions were measured by Western blot.Results: The A-value and early apoptosis rate, apoptosis rate and S-phase percentage, and protein expressions of NF-κB, MCP-1, IL-6, IL-2, TNF-ɑ, Bax, Cyt-C, caspase-3, TGF-β1, and p-Smad3 of MC cells in the HGG at 12 h, 24 h and 48 h were higher than those in the CNG. The above indices were lower in the WMG, and Qijin granules 1/2/3 groups than in the HGG. The Bcl-2, Smad7 protein expression level and the percentage of G1 and G2/M phase were lower in the HGG than in the CNG, and the above indeices were higher in the WMG and Qijin granules 1/2/3 group than in HGG.Conclusion: Qijin granules can dose-dependently inhibit high glucose-induced proliferation and apoptosis in rat MC cells, block the cell cycle and reduce inflammatory responses. This may be related to the regulation of NF-κB, MCP-1 and TGF-β1/Smad signaling pathways. These findings provide theoretical and experimental basis for the clinical treatment of early diabetic nephropathy.

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“…Intriguingly, PKCβ2 knockdown inhibited the expression levels of pERK, JNK and p38. Therefore, PKCβ2 knockdown weakens ERK/JNK/p38 pathway activation in meglumine diatrizoate and AGEs-induced HK-2 cells (24,25). Autophagy is a key biological phenomenon involved in the development and growth of organisms (26).…”

Section: Discussionmentioning

confidence: 99%

Inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy

Jiang¹,

Zhao²,

Ye³

et al. 2020

Ann Transl Med

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Background: Contrast induced diabetic nephropathy (CIN) is an important cause of hospital-acquired acute renal failure. Our aim was to observe the effect of protein kinase C β2 (PKCβ2) knockdown on human proximal tubular epithelial cells (HK-2 cells) against meglumine diatrizoate and advanced glycation end products (AGEs)-induced apoptosis and autophagy.Methods: Cell viability was detected using cell counting kit-8 (CCK-8) assay in HK-2 cells after disposal with meglumine diatrizoate and AGEs with or without PKCβ2 siRNA/inhibitor LY333531. Flow cytometry and western blot were used to test cell apoptosis and the related protein levels in meglumine diatrizoate and AGEs co-treated HK-2 cells with or without PKCβ2 siRNA/inhibitor LY333531. Autophagy related proteins were detected using western blot. Immunofluorescence staining was used to examine the autophagyspecific protein light chain 3 (LC3), and autophagosome and autolysosome formation was observed under a transmission electron microscopy.Results: CCK-8 assay results showed that meglumine diatrizoate inhibited AGEs-induced HK-2 cell viability. Furthermore, meglumine diatrizoate promoted cell apoptosis and the expression level of caspase3 in AGEs-induced HK-2. Western blot results showed that meglumine diatrizoate elevated the expression levels of PKCβ2 and p-PKCβ2 in AGEs-induced HK-2 cells, and up-regulated the expression level of Beclin-1 and the ratio of LC3 II/LC3 I, and down-regulated the expression level of p62 in AGEs-induced HK-2 cells. We found that PKCβ2 knockdown alleviated meglumine diatrizoate and AGEs-induced HK-2 cell apoptosis and autophagy. Intriguingly, PKCβ2 inhibitor LY333531 reversed 3-methyladenine (3-MA)-induced autophagy inhibition in meglumine diatrizoate and AGEs-induced HK-2 cells.Conclusions: Our findings reveal that inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy, which provide a novel therapeutic insight for CIN in diabetic patients.

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High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Cited by 14 publications

References 34 publications

Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis

Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis

Effects of Qijin granules on high glucose-induced proliferation, apoptosis and expression of nuclear factor- κB and MCP-1 in rat glomerular mesangial cells

Inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy

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