miR-27b represses migration of mouse MSCs to burned margins and prolongs wound repair through silencing SDF-1a

• Published in: PloS one 2013-07, Vol.8 (7), p.e68972-e68972
• Main Authors: Lü, Mu-Han, Hu, Chang-Jiang, Chen, Ling, Peng, Xi, Chen, Jian, Hu, Jiong-Yu, Teng, Miao, Liang, Guang-Ping
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Animal tissues; Animals; Binding; Bioinformatics; Biology; Bone marrow; Burns; Burns - genetics; Burns - pathology; Burns - physiopathology; Cell migration; Cell Movement - genetics; Chemokine CXCL12 - deficiency; Chemokine CXCL12 - genetics; Chemotaxis; Comparative analysis; Computational Biology; Correlation; Correlation analysis; CXCR4 protein; Down-Regulation; Enzyme-linked immunosorbent assay; Enzymes; Epidermis; Female; Fluorescence; Gastroenterology; Gene expression; Gene Silencing; Genetic engineering; Genomes; Green fluorescent protein; Hot Temperature; House mouse; Immunohistochemistry; Laboratory animals; Male; Medical research; Mesenchymal stem cells; Mesenchymal Stromal Cells - pathology; Mesenchyme; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Molecular modelling; Overexpression; Protein binding; Repair; SDF-1 protein; Skin; Skin - pathology; Stem cell transplantation; Stem cells; Transgenic mice; Wound care; Wound healing; Wound Healing - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068972

Interactions between stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 are crucial for the recruitment of mesenchymal stem cells (MSCs) from bone marrow (BM) reservoirs to damaged tissues for repair during alarm situations. MicroRNAs are differentially expressed in stem cell niches, suggesting a specialized role in stem cell regulation. Here, we gain insight into the molecular mechanisms involved in regulating SDF-1α. MSCs from green fluorescent protein transgenic male mice were transfused to irradiated recipient female C57BL/6 mice, and skin burn model of bone marrow-chimeric mice were constructed. Six miRNAs with differential expression in burned murine skin tissue compared to normal skin tissue were identified using microarrays and bioinformatics. The expression of miR-27b and SDF-1α was examined in burned murine skin tissue using quantitative real-time PCR (qPCR) and immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA). The Correlation of miR-27b and SDF-1α expression was analyzed by Pearson analysis Correlation. miRNAs suppressed SDF-1α protein expression by binding directly to its 3'UTR using western blot and luciferase reporter assay. The importance of miRNAs in MSCs chemotaxis was further estimated by decreasing SDF-1α in vivo and in vitro. miR-23a, miR-27a and miR-27b expression was significantly lower in the burned skin than in the normal skin (p