The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells

Feng, Xiaoqin; Liu, Shuxia; Chao, Wu; Pengpeng, Kang; Liu, Qingjuan; Hao, Jun; Li, Hongbo; Li, Fan; Zhang, Yujun; Fu, Xiaohui; Zhang, Sanbing; Zuo, Li

doi:10.1152/ajpcell.00385.2013

Cited by 49 publications

(38 citation statements)

References 26 publications

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“…NF-κB is known to be an important nuclear transcription factor, and plays a predominant role in cell innate immune system [56,57,58]. It has been reported to play central roles in inflammatory response to mycoplasma invasion [4,59,60].…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

Yuan

Zou

Zhao

et al. 2018

IJMS

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Mycoplasma gallisepticum (MG) is the pathogen of chronic respiratory disease (CRD), hallmarked by vigorous inflammation in chickens, causing the poultry industry enormous losses. miRNAs have emerged as important regulators of animal diseases. Previous miRNA sequencing data has demonstrated that miR-130b-3p is up-regulated in MG-infected chicken embryo lungs. Therefore, we aimed to investigate the function of miR-130b-3p in MG infection of chickens. RT-qPCR results confirmed that miR-130b-3p was up-regulated both in MG-infected chicken embryo lungs and chicken embryonic fibroblast cells (DF-1 cells). Furthermore, functional studies showed that overexpression of miR-130b-3p promoted MG-infected DF-1 cell proliferation and cell cycle, whereas inhibition of miR-130b-3p weakened these cellular processes. Luciferase reporter assay combined with gene expression data supported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) was a direct target of miR-130b-3p. Additionally, overexpression of miR-130b-3p resulted in up-regulations of phosphatidylinositol-3 kinase (PI3K), serine/threonine kinase (AKT), and nuclear factor-κB (NF-κB), whereas inhibition of miR-130b-3p led to the opposite results. Altogether, upon MG infection, up-regulation of miR-130b-3p activates the PI3K/AKT/NF-κB pathway, facilitates cell proliferation and cell cycle via down-regulating PTEN. This study helps to understand the mechanism of host response to MG infection.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

Yuan

Zou

Zhao

et al. 2018

IJMS

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“…FOXC1 has been shown to activate the PI3K/AKT signaling pathway [49]. The PI3K enzyme acts on membrane PI and activates Akt to phosphorylate several downstream proteins, such as NF-κB and GSK3-β [50]. Through the PI3K/AKT signaling pathway, FOXC1 is able to promote the epithelial-to-mesenchymal transition in cervical carcinoma [49].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

Liu¹,

Miao²,

Gào³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.

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“…The PI3K/AKt/mTOR signal pathway takes part in a variety of cellular functions, including cell survival, cell growth and protein synthesis (Sarbassov et al, ; Garcia et al, ; Feng et al, ). Studies indicate that HMGB1, by activating the PI3K/Akt signal pathway induced the proliferation of mouse mesangial cells (Feng et al, ; Feng et al, ). Our data showed that IgA1 from HSP patients activated ERK1/2 and PI3K/AKt/mTOR signals in cultured HMCs, and IgA1‐induced activation of ERK1/2 and PI3K/AKt/mTOR was inhibited by the human TfR polyclonal antibody (hTfR pAb) and sTfR, indicating the signals involved in the HMCs proliferation induced by IgA1 from HSP.…”

Section: Discussionmentioning

confidence: 99%

IgA1 isolated from Henoch‐Schönlein purpura children promotes proliferation of human mesangial cells in vitro

Zhang

Yan

Chen

et al. 2019

Cell Biology International

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Previous studies show that the proliferation of human mesangial cells (HMCs) played a significant part in the pathogenesis of Henoch‐Schönlein purpura nephritis (HSPN). The aim of this study was to explore the proliferation of HMCs induced by IgA1 isolated from the sera of HSP patients. HMCs were cultured in three different types of media, including IgA1 from patients with HSP (HSP IgA1 group), healthy children (healthy IgA1 group) and medium (control group). The proliferation of HMCs incubated with IgA1 was determined by cell counting kit‐8 assay and bromodeoxyuridine incorporation. The expression of ERK1/2 and phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of the rapamycin (PI3K/AKt/mTOR) signals and transferrin receptor (TfR/CD71) was detected with the methods of immunoblotting. The results indicated that the proliferation of HMCs significantly increased in the HSP IgA1 group compared with that in the control group or the healthy IgA1 group (P < 0.001). Moreover, we found that IgA1 isolated from HSP patients activated ERK and PI3K/AKt/mTOR signals, and markedly increased TfR/CD71 expression in HMCs. These effects induced by IgA1 isolated from patients with HSP were inhibited by human TfR polyclonal antibody (hTfR pAb) and soluble human transferrin receptor (sTfR), indicating that IgA1‐induced HMC proliferation and ERK1/2 and PI3K/AKt/mTOR activation were dependent on TfR/CD71 engagement. Altogether, these data suggested that TfR/CD71 overexpression and ERK1/2 and PI3K/AKt/mTOR activation were engaged in HMC proliferation induced by IgA1 from HSP patients, which might be related to the mesangial injury of HSPN.

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The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells

Cited by 49 publications

References 26 publications

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

IgA1 isolated from Henoch‐Schönlein purpura children promotes proliferation of human mesangial cells in vitro

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