miR-27b Represses Migration of Mouse MSCs to Burned Margins and Prolongs Wound Repair through Silencing SDF-1aReport as inadecuate




miR-27b Represses Migration of Mouse MSCs to Burned Margins and Prolongs Wound Repair through Silencing SDF-1a - Download this document for free, or read online. Document in PDF available to download.

Background

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.

Methods

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.

Results

miR-23a, miR-27a and miR-27b expression was significantly lower in the burned skin than in the normal skin p<0.05. We also found that several miRNAs suppressed SDF-1α protein expression, while just miR-27a and miR-27b directly bound to the SDF-1α 3′UTR. Moreover, the forced over-expression of miR-27a and miR-27b significantly reduced the directional migration of mMSCs in vitro. However, only miR-27b in burn wound margins significantly inhibited the mobilization of MSCs to the epidermis.

Conclusion

miR-27b may be a unique signature of the stem cell niche in burned mouse skin and can suppress the directional migration of mMSCs by targeting SDF-1α by binding directly to its 3′UTR.



Author: Mu-Han Lü , Chang-Jiang Hu , Ling Chen, Xi Peng, Jian Chen , Jiong-Yu Hu, Miao Teng, Guang-Ping Liang

Source: http://plos.srce.hr/



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