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Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromalcells

Title
Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromalcells
Author
채영규
Keywords
mesenchymal stem cells (MSCs); Toll-like receptor (TLR); gene expression; cell migration; transcriptomics; forkhead box protein O; polyinosinic:polycytidylic acid; RNA-sequencing
Issue Date
2019-04
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v. 294, NO 21, Page. 8424-8437
Abstract
Mesenchymal stromal cells (MSCs) can potently regulate the functions of immune cells and are being investigated for the management of inflammatory diseases. Toll-like receptor 3 (TLR3)-stimulated human MSCs (hMSCs) exhibit increased migration and chemotaxis within and toward damaged tissues. However, the regulatory mechanisms underlying these migratory activities are unclear. Therefore, we analyzed the migration capability and gene expression profiles of TLR3-stimulated hMSCs using RNA-Seq, wound healing, and transwell cell migration assay. Along with increased cell migration, the TLR3 stimulation also increased the expression of cytokines, chemokines, and cell migration-related genes. The promoter regions of the latter showed an enrichment of putative motifs for binding the transcription factors forkhead box O1 (FOXO1), FOXO3, NF-kB (NF-kB1), and RELA proto-oncogene and NF-kB subunit. Of note, FOXO1 inhibition by the FOXO1-selective inhibitor AS1842856 significantly reduced both migration and the expression of migration-related genes. In summary, our results indicate that TLR3 stimulation induces hMSC migration through the expression of FOXO1-activated genes. © 2019 American Society for Biochemistry and Molecular Biology Inc. All rights reserved.
URI
http://www.jbc.org/content/294/21/8424http://repository.hanyang.ac.kr/handle/20.500.11754/110907
ISSN
0021-9258; 1083-351X
DOI
10.1074/jbc.RA119.008673
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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