MicroRNA‐194 overexpression protects against hypoxia/reperfusion‐induced HK‐2 cell injury through direct targeting Rheb

Shen, Yan; Zhao, Yan; Wang, Lijun; Zhang, Wenjing; Liu, Chao; Yin, Aiping

doi:10.1002/jcb.28114

Cited by 25 publications

(19 citation statements)

References 37 publications

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“…To simulate renal H/R models in vitro, HK-2 cells were treated by H/R. In detail, HK-2 cells were firstly cultured in hypoxia conditions containing 1% O 2 , 5% CO 2 , and 94% N 2 for 24 h, and then, cells were subject to 21% O 2 for 12 h [ 40 ]. The control cells were maintained in normal atmosphere with 95% air and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Silence of Long Noncoding RNA SNHG14 Alleviates Ischemia/Reperfusion‐Induced Acute Kidney Injury by Regulating miR‐124‐3p/MMP2 Axis

Xue

Liu

Wang

et al. 2021

BioMed Research International

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Purpose. Ample evidence has proved that lncRNAs are pivotal regulators in acute kidney injury (AKI). Here, we focus on the role and mechanism of lncRNA SNHG14 in ischemia/reperfusion- (I/R-) caused AKI. Methods. I/R and hypoxia/reoxygenation (H/R) were applied to induce rats and HK-2 cells to establish AKI models in vivo and in vitro. Relative expression of SNHG14, miR-124-3p, and MMP2 was determined by qRT-PCR. HE staining was used to evaluate pathological changes in renal tissues, and acute tubular necrosis (ATN) score was calculated. Renal function was evaluated by measuring serum creatinine content and blood urea nitrogen content. Levels of IL-1β, IL-6, and TNF-α were measured by ELISA. Cell viability was examined by MTT assay. Oxidative stress was assessed by measuring SOD, MDA, and ROS levels. The target of SNHG14 or miR-124-3p was verified by DLR assay. Protein expression of MMP2 was examined by western blot. Results. SNHG14 was boosted in renal tissues of I/R-stimulated rats and H/R-induced HK-2 cells, while miR-124-3p was diminished in H/R-stimulated HK-2 cells. Si-SNHG14 or miR-124-3p mimics repressed inflammation and oxidative stress and enhanced cell viability in H/R-stimulated HK-2 cells. Sh-SNHG14 mitigated I/R-induced AKI in rats. MiR-124-3p was targeted by SNHG14, and MMP2 was targeted by miR-124-3p. Inhibition of miR-124-3p or upregulation of MMP2 reversed inhibitory effects of SNHG14 silence on inflammation and oxidative stress as well as the promoting effect of SNHG14 silence on cell viability in H/R-induced HK-2 cells. Conclusion. Knockdown of SNHG14 alleviated I/R-induced AKI by miR-124-3p-mediated downregulation of MMP2.

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Section: Methodsmentioning

confidence: 99%

Silence of Long Noncoding RNA SNHG14 Alleviates Ischemia/Reperfusion‐Induced Acute Kidney Injury by Regulating miR‐124‐3p/MMP2 Axis

Xue

Liu

Wang

et al. 2021

BioMed Research International

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“…miR-146 can prevent injury in I/R by targeting IGSF1 and exert a renal protective effect [13]. In addition, miR-194 overexpression can reduce hypoxia/reperfusion-triggered HK-2 cell injury by regulating Rheb [14]. miR-195-5p belongs to the microRNA-15a/b/16/195/497 family [15].…”

Section: Introductionmentioning

confidence: 99%

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

Jiang

Zhong

et al. 2020

Aging

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Acute kidney injury (AKI) is a common renal dysfunction. Renal ischemia-reperfusion (I/R) injury contributes to AKI progression. The microRNA miR-195-5p can act as a crucial tumor inhibitor in various cancers. However, the potential biological effects of miR-195-5p on AKI are not well-understood. We found that miR-195-5p levels were decreased in the serum samples of patients with AKI. Next, we determined miR-195-5p expression in the renal tissues of the rats and found that it was downregulated. Renal function was evaluated and confirmed using blood urea nitrogen and serum Cr levels. In parallel, the hypoxia-induced NRK-52E cell model was employed, and miR-195-5p was found to be markedly reduced under hypoxic conditions. Furthermore, miR-195-5p was modulated in NRK-52E cells. miR-195-5p induced NRK-52E cell proliferation and protected NRK-52E cells against hypoxia-triggered apoptosis. In an I/R mouse model, miR-195-5p alleviated renal injury triggered by I/R. In addition, oxidative stress and inflammatory factor concentrations were assessed using ELISA. The results showed that miR-195-5p mimicked attenuated oxidative stress induced by I/R injury and downregulated the protein expression of inflammatory factors. Moreover, we identified that vascular endothelial growth factor A (VEGFA) was a target gene of miR-195-5p, which could negatively regulate VEGFA expression in vitro. Inhibitors of miR-195-5p subsequently contributed to renal injury, which was reversed by VEGFA loss. In conclusion, miR-195-5p may repress AKI by targeting VEGFA.

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“…Moreover, miR-194 has been identified to relieve inflammatory response through inhibition of the TGF-β/SMAD signaling pathway activation in chronic idiopathic urticarial [12]. Besides, in renal ischemia-reperfusion injury, upregulation of miR-194 can restrain the secretion of proinflammatory cytokines such as IL-1β, IL-6 and TNF-α [13]. However, the regulatory mechanism of miR-194 on inflammatory response of ALI is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Suppressed nuclear factor-kappa B alleviates lipopolysaccharide-induced acute lung injury through downregulation of CXCR4 mediated by microRNA-194

et al. 2020

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Acute lung injury (ALI) is a highly lethal pulmonary disease that causes edema, hypoxemia and respiratory failure. Recent evidence indicates that nuclear factor-kappa B (NF-κB) plays a crucial role in ALI development. However, the regulatory mechanism of NF-κB on ALI remains enigmatic. In this study, we investigated potential molecular mechanism of NF-κB on ALI induced by lipopolysaccharide (LPS). BALB/c mice were subjected to intratracheal spraying of LPS to generate an ALI mode, with the activity of NF-κB in mice tissues being detected by enzyme linked immunosorbent assay (ELISA), and the number of inflammatory cells in bronchoalveolar lavage fluid being counted. Then, the macrophage cell line RAW264.7 exposed to LPS were treated with ammonium pyrrolidinedithiocarbamate (PDTC) (inhibitor of NF-κB), miR-194 mimic, or oe-chemokine receptor type 4 (CXCR4) separately or in combination. After that, ELISA and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression level of IL-1β, IL-6, TNF-α, miR-194 and CXCR4, respectively. In addition, the targeting relationship between miR-194 and CXCR4 was verified by dual-luciferase reporter gene assay. The dry/ wet ratio of lung and the MPO activity were also measured to assess the inflammatory response in mice. Activation of NF-κB down-regulated the miR-194 expression in LPS-induced ALI. Overexpression of miR-194 alleviated LPSinduced ALI and reduced the expression of inflammatory factors IL-1β, IL-6 and TNF-α via targeting CXCR4. In LPSinduced ALI, NF-κB mediates the CXCR4 expression by inhibiting the expression of miR-194, thus promoting the inflammatory injury of lung.

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MicroRNA‐194 overexpression protects against hypoxia/reperfusion‐induced HK‐2 cell injury through direct targeting Rheb

Cited by 25 publications

References 37 publications

Silence of Long Noncoding RNA SNHG14 Alleviates Ischemia/Reperfusion‐Induced Acute Kidney Injury by Regulating miR‐124‐3p/MMP2 Axis

Silence of Long Noncoding RNA SNHG14 Alleviates Ischemia/Reperfusion‐Induced Acute Kidney Injury by Regulating miR‐124‐3p/MMP2 Axis

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

Suppressed nuclear factor-kappa B alleviates lipopolysaccharide-induced acute lung injury through downregulation of CXCR4 mediated by microRNA-194

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