MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4

Dong, Hang; Jiang, Guangyu; Zhang, Jiayue; Kang, Yu-Ming

doi:10.1159/000513506

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…HRD1 KO decreased VSMC contractile marker α-SMA, RNA-seq also revealed the upregulated KLF4 expression (Fig. 4E), which is the VSMC dedifferentiation marker 43 . Furthermore, we validated the proliferation and migration ability in HRD1-KO VSMCs, as shown in Fig.…”

Section: Discussionmentioning

confidence: 80%

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress

Wang,

Ren,

et al. 2023

Mol Cell Biochem

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Aims: Phenotypic change of vascular smooth muscle cells (VSMCs) contributes a lot in obesity induced vascular pathological remodeling. The endoplasmic reticulum (ER) is critical for maintaining VSMC function, but the accumulation of misfolded proteins in the ER impairs cell function. As the major ER protein quality control responsible for clearing misfolded proteins, ER-associated degradation (ERAD) whose key member is HRD1 plays vital role in lipid metabolism, but its function in VSMC phenotypic change remains poorly understood.Main methods: The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The HE and EVG (VERHOEFF'S VAN GIESON) staining were used to demonstrate vascular pathological changes. Cripr and transcriptomic analysis were applied in in vitro studies to explore the cellular mechanism. Key ndings: Data showed a signi cant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol treatment.Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 de ciency increased the expression of genes related with ER stress, proliferation, and migration, but decreased the VSMC contractile-related genes. HRD1 de ciency in VSMCs also exacerbated the proliferation, migration, and ROS production induced by cholesterol, which promoted the VSMC phenotypic change process.Signi cance: Our results proved that HRD1 plays an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress. Thus, HRD1 may have the potential to be a therapeutic target in lipid metabolic disorders induced vascular remodeling caused by VSMC phenotypic change. HighlightsWe proved HRD1 KO exacerbated the proliferation, migration, and ROS production induced by cholesterol, promoted the VSMCs transfer from a contractile phenotype to a synthetic phenotype, our study provided a new target in treating the vascular pathological remodeling caused by VSMC phenotypic change.University, as well as the Animal Laboratory Administration Center and Ethics Committee of the Sun Yat-Sen University, the third a liated hospital. Male C57Bl6/J mice were purchased from the Guangdong Medical Laboratory Animal center. The persistent ID is SYSU-IACUC-2022-001869. All mice were maintained in a SPF environment with controlled humidity and temperature (22 ± 2°C) under a 12 h:12 h light/dark cycle and received water and a chow diet (CD) ad libitum. At 2 months of age, the mice were divided to receive CD (3.86 kcal/g), or HFD (a very high fat, 60% calories from fat; 5.55 kcal/g diet) for 4 months. Manipulations of Cultured VSMCsHuman primary VSMCs were purchased from Guangzhou BIOSPECIES Company (batch number 20220704), shown in Table SI, cultured in DMEM containing 10% fetal bovine serum and antibiotics (1% ER: endoplasmic reticulum VSMC: vascular smooth muscle cell ERAD: endoplasmic reticulum-associated degradation UPR: unfolded protein response

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Section: Discussionmentioning

confidence: 80%

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress

Wang,

Ren,

et al. 2023

Mol Cell Biochem

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“…Herein, we found that miR-506-3p combined with circ_0003928. As reported early, miR-506-3p regulates the progression of cancer [27], atherosclerosis [28], bronchial asthma [29] and cardiovascular disease [30]. In particular, miR-506-3p combined with long noncoding RNA KCNQ1OT1 (lncRNA KCN-Q1OT1) to regulate HK-2 cell oxidative stress and pyroptosis [17].…”

Section: Discussionmentioning

confidence: 87%

Knockdown of circ_0003928 ameliorates high glucose-induced dysfunction of human tubular epithelial cells through the miR-506-3p/HDAC4 pathway in diabetic nephropathy

Liu

Cui²,

Ding

et al. 2022

Eur J Med Res

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Background Previous data have indicated the importance of circular RNA (circRNA) in the pathogenesis of diabetic nephropathy (DN). The study is designed to investigate the effects of circ_0003928 on oxidative stress and apoptosis of high glucose (HG)-treated human tubular epithelial cells (HK-2) and the underlying mechanism. Methods The DN cell model was established by inducing HK-2 cells using 30 mmol/L D-glucose. RNA expression of circ_0003928, miR-506-3p and histone deacetylase 4 (HDAC4) was detected by quantitative real-time polymerase chain reaction. Cell viability and proliferation were investigated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine (EdU) assays, respectively. Oxidative stress was evaluated by commercial kits. Caspase 3 activity and cell apoptotic rate were assessed by a caspase 3 activity assay and flow cytometry analysis, respectively. Protein expression was detected by Western blotting analysis. The interactions among circ_0003928, miR-506-3p and HDAC4 were identified by dual-luciferase reporter and RNA pull-down assays. Results Circ_0003928 and HDAC4 expression were significantly upregulated, while miR-506-3p was downregulated in the serum of DN patients and HG-induced HK-2 cells. HG treatment inhibited HK-2 cell proliferation, but induced oxidative stress and cell apoptosis; however, these effects were reversed after circ_0003928 depletion. Circ_0003928 acted as a miR-506-3p sponge, and HDAC4 was identified as a target gene of miR-506-3p. Moreover, the circ_0003928/miR-506-3p/HDAC4 axis regulated HG-induced HK-2 cell dysfunction. Conclusion Circ_0003928 acted as a sponge for miR-506-3p to regulate HG-induced oxidative stress and apoptosis of HK-2 cells through HDAC4, which suggested that circ_0003928 might be helpful in the therapy of DN.

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“…Among these SNHG1-related miRNAs and target genes, the binding site of SNHG16 to miR-506-3p was identified. In addition, studies have also shown that miR-506-3p is up-regulated in vascular smooth muscle, affecting the proliferation, migration, differentiation and contraction of vascular smooth muscle cells [ 29 ]. Therefore, it was hypothesized that SNHG16 may be involved in the alteration of biological behavior of KIRC cells through miR-506-3p.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis

Cheng,

Gu,

et al. 2024

Heliyon

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MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4

Cited by 8 publications

References 21 publications

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress

Knockdown of circ_0003928 ameliorates high glucose-induced dysfunction of human tubular epithelial cells through the miR-506-3p/HDAC4 pathway in diabetic nephropathy

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis

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