Dataset Information

CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis.

ABSTRACT: In this study, we investigated the role of circular RNA_30032 (circRNA_30032) in renal fibrosis and the underlying mechanisms. The study was carried out using TGF-β1-induced BUMPT cells and unilateral ureteral obstruction (UUO)-induced mice, respectively, as in vitro and in vivo models. CircRNA_30032 expression was significantly increased by 9.15- and 16.6-fold on days 3 and 7, respectively, in the renal tissues of UUO model mice. In TGF-β1-treated BUMPT cells, circRNA_30032 expression was induced by activation of the p38 mitogen-activated protein kinase signaling pathway. Quantitative real-time PCR, western blotting and dual luciferase reporter assays showed that circRNA_30032 mediated TGF-β1-induced and UUO-induced renal fibrosis by sponging miR-96-5p and increasing the expression of profibrotic proteins, including HBEGF, KRAS, collagen I, collagen III and fibronectin. CircRNA_30032 silencing significantly reduced renal fibrosis in UUO model mice by increasing miR-96-5p levels and decreasing levels of HBEGF and KRAS. These results demonstrate that circRNA_30032 promotes renal fibrosis via the miR-96-5p/HBEGF/KRAS axis and suggest that circRNA_30032 is a potential therapeutic target for treatment of renal fibrosis.

SUBMITTER: Yi L

PROVIDER: S-EPMC8148471 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis.

Yi Lei L Ai Kai K Li Huiling H Qiu Shuangfa S Li Yijian Y Wang Yinhuai Y Li Xiaozhou X Zheng Peilin P Chen Junxiang J Wu Dengke D Xiang Xudong X Chai Xiangping X Yuan Yunchang Y Zhang Dongshan D

Aging 20210511 9

In this study, we investigated the role of circular RNA_30032 (circRNA_30032) in renal fibrosis and the underlying mechanisms. The study was carried out using TGF-β1-induced BUMPT cells and unilateral ureteral obstruction (UUO)-induced mice, respectively, as <i>in vitro</i> and <i>in vivo</i> models. CircRNA_30032 expression was significantly increased by 9.15- and 16.6-fold on days 3 and 7, respectively, in the renal tissues of UUO model mice. In TGF-β1-treated BUMPT cells, circRNA_30032 expres ...[more]

PMID: 33973871

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Project description:Acute kidney injury and chronic renal fibrosis are intractable pathological processes to resolve, yet limited strategies are able to effectively address them. Cardamonin (CAD) is a flavonoid with talented antioxidant, anti-inflammatory capacity, and satisfactory biosafety. In our study, animal and cellular models of renal ischemia/reperfusion (I/R) and unilateral ureteral obstruction (UUO) were successfully constructed to confirm whether CAD confers protective effects and underlying mechanisms. Animal experiments demonstrated that CAD application (100 mg/kg) distinctly ameliorated tissue damage and improved renal function. Meanwhile, the continuous oral administration of CAD after UUO surgery efficiently inhibited renal fibrosis as confirmed by hematoxylin-eosin (H&E), Sirius red, and Masson staining as well as the downregulated mRNA and protein expression of collagen I, α-smooth muscle actin (α-SMA), collagen III, and fibronectin. Interestingly, in transforming growth factor β1 (TGF-β1)-stimulated and hypoxia/reoxygenation (H/R)-exposed human kidney-2 (HK-2) cells, protective effects of CAD were again authenticated. Meanwhile, we performed bioinformatics analysis and constructed the "ingredient-target-pathway-disease" network to conclude that the potential mechanisms of CAD protection may be through the regulation of oxidative stress, inflammation, apoptosis, and mitogen-activated protein kinase (MAPK) pathway. Furthermore, experimental data validated that CAD evidently decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) content while depressing the mRNA and protein expression of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Il-1β) and inhibiting apoptosis as evidenced by decreased levels of P53, BAX, cleaved caspase-3, and apoptotic rate in renal I/R and UUO models. In addition, the impact of CAD on restraining oxidative stress and inflammation was attributed to its ability to elevate antioxidant enzyme activities including catalase, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) and to inhibit the inflammation-associated MARK/nuclear factor-κB (MAPK/NF-κB) signaling pathway. In conclusion, cardamonin restored the antioxidative capacity to block oxidative stress and suppressed the MAPK/NF-κB signaling pathway to alleviate inflammatory response, thus mitigating I/R-generated acute kidney injury/UUO-induced renal fibrosis in vivo and in vitro, which indicated the potential therapeutic advantage of cardamonin in attenuating acute and chronic kidney injuries.

Dataset Information

CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis.

Publications

CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis.

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