MiR-200b attenuates IL-6 production through IKKβ and ZEB1 in human gingival fibroblasts

Matsui, Sari; Zhou, Liming; Nakayama, Yohei; Mezawa, Masaru; Kato, Ayako; Suzuki, Naoto; Tanabe, Natsuko; Nakayama, Tomohiro; Suzuki, Yuki; Kamio, Noriaki; Takai, Hideki; Ogata, Yorimasa

doi:10.1007/s00011-018-1192-1

Cited by 23 publications

(24 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given its inflammatory potential, the NF-κB signaling pathway is tightly regulated by proteins including inhibitor of NF-κB alpha (IκBα), which prevents NF-κB nuclear translocation and transcriptional activation until immunoproteasome-mediated IκBα degradation occurs (Suryavanshi & Kulkarni, 2017;Zhu, Han, Yuan, Xue, & Pang, 2018). The IKK complex is composed of three subunits each encoded by a separate gene, including IKKα, IKKβ, and IKKγ (Ben et al, 2019;Matsui et al, 2018); in which, IKKβ is critical for the production of inflammatory cytokines and associated with the activation of cancers, including breast cancer, pancreatic cancer, melanoma, and acute myeloid leukemia (Greten et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Guo

Cai

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is a common clinically relevant complication of diabetes that is associated with damage to the capillaries, yet the etiology of this condition remains unclear. Nuclear factor-kappa B (NF-κB) activation is known to be associated with DN-related inflammation and disease progression. Recent work indicated that microRNAs are diagnostic biomarkers of DN progression associated with inflammation in the progression of DN. miR-218 is known to play key regulatory roles in certain cancers in humans, while its influence on DN pathology remains uncertain.The present study, therefore, sought to assess how miR-218 influences the progression of disease in both a rat streptozotocin-induced model of DN and as well as an in vitro model system in which mouse podocytes were stimulated with high glucose levels. We found miR-218 to be markedly downregulated in both model systems relative to appropriate controls, and this downregulation was associated with IKK-β upregulation. In DN rat model, overexpressing miR-218 was sufficient to reduce renal injury. We further determined that podocyte proliferation was markedly impaired by glucose treatment, leading to the apoptotic death of these cells, and miR-218 mimics were able to reduce these phenotypes. Overexpressing miR-218 also significantly dampened inflammatory responses in this model system, as evidenced by reduced tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and MCP-1 levels. We then confirmed that miR-218 targeting the messenger RNA encoding IKK-β using a dual-luciferase reporter assay. Together, our results provide clear evidence that miR-218 regulate NF-κB-mediated inflammation, which is central to DN progression.

show abstract

Section: Introductionmentioning

confidence: 99%

miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Guo

Cai

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…The miR-200 family, including miR-429, has been studied for its biological function and aberrant expression in various diseases, particularly in tumors (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)35,36). Although several studies demonstrate that miR-429 exerted anti-inflammatory activities in some diseases (35,36), further investigation is necessary to fully understand its biological Figure 4.…”

Section: Discussionmentioning

confidence: 99%

“…Among miRNAs, miR-429, a member of miR-200 family, is studied as an epithelial mesenchymal transition-associated miRNA and is often found to be dysregulated in various types of malignant tumors including oral squamous cell carcinoma (16)(17)(18)(19). Previous studies have reported that miR-429 and its family miRNAs suppress the expression of multiple genes involved in inflammatory signaling and production of interleukins, particularly IL-8 (16)(17)(18)(20)(21)(22)(23)(24)(25)(26)(27). The evidence for the relevance and function of miR-429 in pathological and physiological events has accumulated; however, the possible association of miR-429 with oral inflammatory processes remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Anti‑inflammatory role of microRNA‑429 in human gingival epithelial cells‑inhibition of IL‑8 production through direct binding to IKKβ mRNA

Kawasaki

Amano

2021

Mol Med Rep

View full text Add to dashboard Cite

MicroRNAs (miRNAs), a family of small non-coding RNAs, serve a pivotal role in the regulation of the inflammation by modulating the expression of various genes. However, the molecular mechanism by which miRNAs regulate inflammation-associated molecules in oral epithelial cells remains to be elucidated. The present study examined the biological function of miR-429 by performing the gain-/loss-of-function studies of miR-429 in a gingival squamous cell carcinoma line Ca9-22 cells that either over-or under-expressed miR-429 through transient transfection with miR-429 mimic or miR-429 inhibitor, respectively. The results demonstrated that the over-expression of miR-429 suppressed the mRNA level of several interleukins, including IL-8. In addition, the over-expression of miR-429 reduced IL-8 secretion under the basal and TNF-α stimulated conditions, whereas the secretion of IL-8 was enhanced when miR-429 was under-expressed. The over-expression of miR-429 inhibited the activation of the transcription factor NF-κB. Furthermore, we found that miR-429 suppressed both mRNA and protein levels of IKKβ via its direct binding to the 3'-untranslated region of IKKβ mRNA. In addition, the downregulation of IKKβ by small interfering RNA reduced both NF-kB activity and IL-8 production in Ca9-22 cells. Taken together, the findings revealed the molecular mechanism of miR-429 to regulate the inflammatory mediator in gingival cells and suggested that it could be useful as a therapeutic target of oral inflammatory diseases.

show abstract

“…ZEB1 is involved also in inflammatory processes. Suppression of ZEB1 by miR‐200b leads to a decrease in IL‐6 production in gingival fibroblasts …”

Section: Introductionmentioning

confidence: 99%

“…Suppression of ZEB1 by miR-200b leads to a decrease in IL-6 production in gingival fibroblasts. 24 Little is known about ZEB1 expression in oral diseases. TWIST1 and ZEB1 are upregulated in oral submucous fibrosis, which is a potentially malignant condition.…”

mentioning

confidence: 99%

Alterations in the expression of EMT‐related proteins claudin‐1, claudin‐4 and claudin‐7, E‐cadherin, TWIST1 and ZEB1 in oral lichen planus

Hämäläinen

Soini

Pasonen‐Seppänen

et al. 2019

J Oral Pathology Medicine

View full text Add to dashboard Cite

Background Oral lichen planus (OLP) is a chronic T‐cell‐mediated inflammatory disease, which is associated with increased risk of developing oral squamous cell carcinoma. Epithelial‐to‐mesenchymal transition is a physiological phenomenon occurring during growth and organogenesis, but it has also an important role in tumorigenesis. In the present work, we studied the expression of known epithelial‐to‐mesenchymal transition markers in oral lichen planus. Methods In total, 54 oral lichen planus and 22 control samples were analyzed for epithelial‐to‐mesenchymal transition markers. Samples were immunohistochemically stained for claudin‐1, claudin‐4 and claudin‐7, cadherin‐1 (E‐cadherin), Twist‐related protein 1 (TWIST1) and zinc finger E‐box‐binding homeobox 1 (ZEB1). Results The expression of claudin‐1, claudin‐4 and E‐cadherin was significantly weaker in oral lichen planus epithelium compared to controls (P < 0.001). The quantity of claudin‐7‐expressing cells (P < 0.001) and claudin‐7 staining intensity (P < 0.05) in the stroma was greater in lichen planus than in control samples. TWIST1 and ZEB1 stainings were negative in the epithelium in both lichen planus and controls. The number of TWIST1‐expressing cells in the stroma was higher in lichen planus than in controls (P < 0.001). There was a statistically significant difference in ZEB1 staining intensity in the stroma between lichen planus and control samples (P < 0.05). Conclusions The data indicate that the expression of claudin‐1, claudin‐4 and E‐cadherin is decreased in oral lichen planus. This may lead to disturbance in epithelial tight junctions, cell‐cell connections and epithelial permeability, contributing to oral lichen planus pathogenesis. Based on the present study, the role of TWIST1 and ZEB1 in oral lichen planus remains unclear.

show abstract

MiR-200b attenuates IL-6 production through IKKβ and ZEB1 in human gingival fibroblasts

Cited by 23 publications

References 51 publications

miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Anti‑inflammatory role of microRNA‑429 in human gingival epithelial cells‑inhibition of IL‑8 production through direct binding to IKKβ mRNA

Alterations in the expression of EMT‐related proteins claudin‐1, claudin‐4 and claudin‐7, E‐cadherin, TWIST1 and ZEB1 in oral lichen planus

Contact Info

Product

Resources

About