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Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling pathway induced by lipopolysaccharide in human adipose stem cells.
PLoS One. 2019; 14(2):e0212063.Plos

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression related to inflammatory responses. Human adipose stem cells are characterized by pluripotent differentiation potential and isolated from adipose tissues. These cells regulate inflammation mainly by interacting with immune cells and affecting the secretion of immune factors; details of this interaction are currently unknown. In the current study, we successfully established an acute inflammation model and a chronic inflammation model involving adipose stem cells. We used high-throughput miRNA microarray analysis to identify miRNAs that were significantly (p < 0.05) differentially expressed during both acute and chronic inflammation. Lipopolysaccharide (LPS) significantly (p < 0.05) reduced the expression of miR-223-3P and miR-2909, while promoting the production of pro-inflammatory cytokines, interleukin (IL) 6, IL-1β, and tumor necrosis factor (TNF)-α via the Toll-like receptor (TLR) 4/TLR2/nuclear factor (NF)-κB/signal transducer and activator of transcription (STAT) 3 signaling pathway in human adipose stem cells. Further, miR-223-3P expression was significantly (p < 0.05) reduced in human adipose stem cells during activation by IL-6 stimulation. The inducible down-regulation of miR-223-3P resulted in the activation of STAT3, which was directly targeted by miR-223-3P. STAT3 directly targeted TLR4 and TLR2, promoting the production of the pro-inflammatory cytokine, IL-6, and formed a positive feedback loop to regulate IL-6 levels. Similarly, TNF-α significantly (p < 0.05) increased the expression of miR-223-3p, with LPS and TLR4/TLR2/NF-κB/STAT3 forming a negative feedback loop to regulate TNF-α levels. In addition, miR-2909, which depends on NF-κB, targeted Krueppel-like factor (KLF) 4 to regulate the levels of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α. We conclude that miR-223-3p and miR-2909 form a complex regulatory network with pro-inflammatory factors and signaling pathways in adipose stem cells stimulated by LPS. These findings will inform the development of therapies against autoimmune and inflammatory diseases.

Authors+Show Affiliations

Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.Department of Pediatrics, Ren Min Hospital of Wuhan University, WuHan, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30807577

Citation

Wu, Juan, et al. "Impact of miR-223-3p and miR-2909 On Inflammatory Factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 Signaling Pathway Induced By Lipopolysaccharide in Human Adipose Stem Cells." PloS One, vol. 14, no. 2, 2019, pp. e0212063.
Wu J, Niu P, Zhao Y, et al. Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling pathway induced by lipopolysaccharide in human adipose stem cells. PLoS ONE. 2019;14(2):e0212063.
Wu, J., Niu, P., Zhao, Y., Cheng, Y., Chen, W., Lin, L., Lu, J., Cheng, X., & Xu, Z. (2019). Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling pathway induced by lipopolysaccharide in human adipose stem cells. PloS One, 14(2), e0212063. https://doi.org/10.1371/journal.pone.0212063
Wu J, et al. Impact of miR-223-3p and miR-2909 On Inflammatory Factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 Signaling Pathway Induced By Lipopolysaccharide in Human Adipose Stem Cells. PLoS ONE. 2019;14(2):e0212063. PubMed PMID: 30807577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1β, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling pathway induced by lipopolysaccharide in human adipose stem cells. AU - Wu,Juan, AU - Niu,Ping, AU - Zhao,Yueqiang, AU - Cheng,Yanyang, AU - Chen,Weiping, AU - Lin,Lan, AU - Lu,Jingmei, AU - Cheng,Xue, AU - Xu,Zhiliang, Y1 - 2019/02/26/ PY - 2018/10/09/received PY - 2019/01/25/accepted PY - 2019/2/27/entrez PY - 2019/2/27/pubmed PY - 2019/11/8/medline SP - e0212063 EP - e0212063 JF - PloS one JO - PLoS ONE VL - 14 IS - 2 N2 - MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression related to inflammatory responses. Human adipose stem cells are characterized by pluripotent differentiation potential and isolated from adipose tissues. These cells regulate inflammation mainly by interacting with immune cells and affecting the secretion of immune factors; details of this interaction are currently unknown. In the current study, we successfully established an acute inflammation model and a chronic inflammation model involving adipose stem cells. We used high-throughput miRNA microarray analysis to identify miRNAs that were significantly (p < 0.05) differentially expressed during both acute and chronic inflammation. Lipopolysaccharide (LPS) significantly (p < 0.05) reduced the expression of miR-223-3P and miR-2909, while promoting the production of pro-inflammatory cytokines, interleukin (IL) 6, IL-1β, and tumor necrosis factor (TNF)-α via the Toll-like receptor (TLR) 4/TLR2/nuclear factor (NF)-κB/signal transducer and activator of transcription (STAT) 3 signaling pathway in human adipose stem cells. Further, miR-223-3P expression was significantly (p < 0.05) reduced in human adipose stem cells during activation by IL-6 stimulation. The inducible down-regulation of miR-223-3P resulted in the activation of STAT3, which was directly targeted by miR-223-3P. STAT3 directly targeted TLR4 and TLR2, promoting the production of the pro-inflammatory cytokine, IL-6, and formed a positive feedback loop to regulate IL-6 levels. Similarly, TNF-α significantly (p < 0.05) increased the expression of miR-223-3p, with LPS and TLR4/TLR2/NF-κB/STAT3 forming a negative feedback loop to regulate TNF-α levels. In addition, miR-2909, which depends on NF-κB, targeted Krueppel-like factor (KLF) 4 to regulate the levels of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α. We conclude that miR-223-3p and miR-2909 form a complex regulatory network with pro-inflammatory factors and signaling pathways in adipose stem cells stimulated by LPS. These findings will inform the development of therapies against autoimmune and inflammatory diseases. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/30807577/Impact_of_miR_223_3p_and_miR_2909_on_inflammatory_factors_IL_6_IL_1β_and_TNF_α_and_the_TLR4/TLR2/NF_κB/STAT3_signaling_pathway_induced_by_lipopolysaccharide_in_human_adipose_stem_cells_ L2 - http://dx.plos.org/10.1371/journal.pone.0212063 DB - PRIME DP - Unbound Medicine ER -