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miRNAs from inflamed gingiva link gene signaling to increased MET expression

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Item Type:Article
Title:miRNAs from inflamed gingiva link gene signaling to increased MET expression
Creators Name:Zheng, L. and Chopra, A. and Weiner, J. and Beule, D. and Dommisch, H. and Schaefer, A.S.
Abstract:Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p, and -30e-5p in gingiva affected by periodontal inflammation. We aimed to determine direct target genes and signaling pathways regulated by these miRNAs to identify processes relevant to gingival inflammatory responses and tissue homeostasis. We transfected miRNA mimics (mirVana) for each of the 7 miRNAs separately into human primary gingival fibroblasts cultured from 3 different donors. Following RNA sequencing, differential gene expression and second-generation gene set enrichment analyses were performed. miRNA inhibition and upregulation was validated at the transcript and protein levels using quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene assays. All 7 miRNAs significantly increased expression of the gene MET proto-oncogene, receptor tyrosine kinase (MET). Expression of known periodontitis risk genes CPEB1, ABCA1, and ATP6V1C1 was significantly repressed by hsa-miR-130a-3p, -144-3p, and -144-5p, respectively. The genes WASL, ENPP5, ARL6IP1, and IDH1 showed the most significant and strongest downregulation after hsa-miR-142-3p, -17-5p, -223-3p, and -30e-5p transfection, respectively. The most significantly regulated gene set of each miRNA related to cell cycle (hsa-miRNA-144-3p and -5p [P(adj) = 4 × 10(-40) and P(adj) = 4 × 10(-6)], -miR-17-5p [P(adj) = 9.5 × 10(-23)], -miR-30e-5p [P(adj) = 8.2 × 10(-18)], -miR-130a-3p [P(adj) = 5 × 10(-15)]), integrin cell surface interaction (-miR-223-3p [P(adj) = 2.4 × 10(-7)]), and interferon signaling (-miR-142-3p [P(adj) = 5 × 10(-11)]). At the end of acute inflammation, gingival miRNAs bring together complex regulatory networks that lead to increased expression of the gene MET. This underscores the importance of mesenchymal cell migration and invasion during gingival tissue remodeling and proliferation in restoring periodontal tissue homeostasis after active inflammation. MET, a receptor of the mitogenic hepatocyte growth factor fibroblast secreted, is a core gene of this process.
Keywords:Cell Cycle, Mesenchymal Cellular Migration, Periodontitis, CPEB1, ABCA1, ATP6V1C1
Source:Journal of Dental Research
Publisher:International & American Associations for Dental Research
Page Range:1488-1497
Date:December 2023
Official Publication:https://doi.org/10.1177/00220345231197984
PubMed:View item in PubMed

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