Isorhynchophylline exerts anti-asthma effects in mice by inhibiting the proliferation of airway smooth muscle cells: The involvement of miR-200a-mediated FOXC1/NF-κB pathway

Zhu, Jinyue; Wang, Weiqing; Wu, Xia

doi:10.1016/j.bbrc.2019.10.178

Cited by 20 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results confirmed that miR-200a-3p promoted differentiation and proliferation of SMSCs, and inhibited apoptosis of SMSCs in chicken. These results are consistent with the role of miR-200a-3p in human cardiac muscle [23] and airway smooth muscle cells [24]. In addition, it was observed that miR-200a-3p is a negative factor affecting cell proliferation in human cancer.…”

Section: Discussionsupporting

confidence: 89%

MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

Yin

Shen

et al. 2020

IJMS

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that play critical post-transcriptional regulatory roles in skeletal muscle development. Chicken is an optimal model to study skeletal muscle formation because its developmental anatomy is similar to that of mammals. In this study, we identified potential miRNAs in the breast muscle of broilers and layers at embryonic day 10 (E10), E13, E16, and E19. We detected 1836 miRNAs, 233 of which were differentially expressed between broilers and layers. In particular, miRNA-200a-3p was significantly more highly expressed in broilers than layers at three time points. In vitro experiments showed that miR-200a-3p accelerated differentiation and proliferation of chicken skeletal muscle satellite cells (SMSCs) and inhibited SMSCs apoptosis. The transforming growth factor 2 (TGF-β2) was identified as a target gene of miR-200a-3p, and which turned out to inhibit differentiation and proliferation, and promote apoptosis of SMSCs. Exogenous TGF-β2 increased the abundances of phosphorylated SMAD2 and SMAD3 proteins, and a miR-200a-3p mimic weakened this effect. The TGF-β2 inhibitor treatment reduced the promotional and inhibitory effects of miR-200a-3p on SMSC differentiation and apoptosis, respectively. Our results indicate that miRNAs are abundantly expressed during embryonic skeletal muscle development, and that miR-200a-3p promotes SMSC development by targeting TGF-β2 and regulating the TGF-β2/SMAD signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 89%

MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

Yin

Shen

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Then the phosphorylation of TAK1 and downstream molecules IKKβ, IκB was activated successively, which nally resulted in the IκB proteasomal degradation and p-p65 nuclear translocation [39]. And in the study of DZNep's role on mice airway smooth muscle cells and human basal-like breast cancer cells, the NF-κB nuclear translocation was promoted via the IκB phosphorylation, which credited to the up-regulated transcription of Foxc1 after the inhibition of EZH2 and subsequent H3K27me3 [12,13]. Hence, we carried out the silence experiment of EZH2 and the data demonstrated that p-IKKα/β, p-IκBα were promoted by the DZNep-EZH2-H3K27me3-Foxc1 axis, which explained the activation and subsequent nuclear translocation of p-p65.…”

Section: Discussionmentioning

confidence: 99%

“…As previously introduced that the inhibition of EZH2 and subsequently down-regulated H3K27me3 resulted in the transcriptional up-regulation of Foxc1, which activates the phosphorylation of the IκB [11][12][13]. We examined the role of DZNep on the EZH2-H3K27me3-Foxc1 axis.…”

Section: Dznep Activated the Nf-kb Signaling Pathway Through The Ezh2-h3k27me3-foxc1 Axismentioning

confidence: 99%

“…However, one study indicated that the inhibition of EZH2-H3K27me3 axis resulted in the transcriptional up-regulation of Foxc1 [11]. Foxc1 had been veri ed to induce the nuclear translocation of NF-κB through promoting the phosphorylation of IκB both in mice airway smooth muscle cells and human basal-like breast cancer cells [12,13] and the PI3K/AKT signaling pathway in Ovalbumin-Induced Asthmatic Mice [14]. Moreover, the nuclear translocation of activated NF-κB was widely acknowledged to upregulate the key downstream regulators like the nuclear factor of activated T cells c1 (NFATc1) [15] and c-Fos [16], which plays important roles in osteoclast formation [17].…”

Section: Introductionmentioning

confidence: 99%

“…Consistent with our hypothesis, our western blotting analyses and immuno uorescence staining of cytoplasm and nuclear proteins showed the enhancement of NF-κB nuclear translocation upon DZNep treatment (Figure3E, F). Previous literature demonstrated that DZNep could upregulate the NF-κB nuclear translocation by promoting the IκB phosphorylation in mice airway smooth muscle cells and human basal-like breast cancer cells[12,13]. After that, we examined the transduction factors of classical NF-κB signaling pathways, which mainly include the inhibitor of nuclear factor kappa-B kinase (IKK), and inhibitor of nuclear factor kappa-B (IκB), and NF-κB.…”

mentioning

confidence: 99%

See 2 more Smart Citations

DZNep Promotes Mouse Bone Defect Healing via Enhancing Both Osteogenesis and Osteoclastogenesis

Cao¹,

He²,

Rong³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: EZH2 (Enhancer of zeste homolog 2) is a novel oncogene that can specifically trimethylate the histone H3 lysine 27 (H3K27me3) to transcriptionally inhibit the expression of downstream tumor-suppressing genes. As a small molecular inhibitor of EZH2, 3-Deazaneplanocin (DZNep) has been widely studied due to the role of tumor suppression. With the roles of epigenetic regulation of bone cells emerged in past decades, the property and molecular mechanism of DZNep on enhancing osteogenesis had been reported and attracted a great deal of attention recently. this study aims to elucidate the role of DZNep on EZH2-H3K27me3 axis and downstream factors during both osteoclasts and osteoblasts formation and the therapeutic possibility of DZNep on bone defect healing.Methods: Bone marrow drived macrophages (BMMs) cells were cultured and their responsiveness to DZNep was evaluated by Cell Counting Kit-8, TRAP staining assay, Bone Resorption Assay, Podosome Actin Belt. Bone marrow drived mesenchymal stem cells (BMSC) were cultured and their responsiveness to DZNep was evaluated by Cell Counting Kit-8, ALP and AR staining assay. The expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), Wnt signaling pathway was determined by qPCR and western blotting. Mouse bone defect models were created, rescued by DZNep injection and the effectiveness was evaluated by X-ray and Micro-CT and Histological staining.Results: Consistent with the previous study that DZNep enhances osteogenesis via Wnt family member 1(Wnt1), Wnt6, and Wnt10a, our results showed that DZNep also promotes osteoblasts differentiation and mineralization through the EZH2-H3K27me3-Wnt4 axis. Furthermore, we identified that DZNep promoted the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation via facilitating the phosphorylation of IKKα/β, IκB, and subsequently NF-κB nuclear translocation, which credit to the EZH2-H3K27me3-Foxc1 axis. More importantly, the enhanced osteogenesis and osteoclastogenesis result in accelerated mice bone defect healing in vivo.Conclusion: DZNep targeting EZH2-H3K27me3 axis facilitated the healing of mice bone defect via simultaneously enhancing osteoclastic bone resorption and promoting osteoblastic bone formation.

show abstract

Treatment with 5-fluoro-2-oxindole Increases the Antinociceptive Effects of Morphine and Inhibits Neuropathic Pain

et al. 2020

View full text Add to dashboard Cite

Isorhynchophylline exerts anti-asthma effects in mice by inhibiting the proliferation of airway smooth muscle cells: The involvement of miR-200a-mediated FOXC1/NF-κB pathway

Cited by 20 publications

References 21 publications

MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

DZNep Promotes Mouse Bone Defect Healing via Enhancing Both Osteogenesis and Osteoclastogenesis

Treatment with 5-fluoro-2-oxindole Increases the Antinociceptive Effects of Morphine and Inhibits Neuropathic Pain

Contact Info

Product

Resources

About