MicroRNA-126 effects on free flap activity by regulating bone marrow mesenchymal stem cells

doi:10.3969/j.issn.2095-4344.2016.36.002

Abstract

Abstract:

BACKGROUND: MicroRNA has tissue and cell specificity, and high expression of endothelial cell-specific microRNA-126 (miR-126) plays an important role in angiogenesis.
OBJECTIVE: To explore the effect of miR-126 on transplanted free flap survival and histological activity as well as its mechanism in angiogenesis.
METHODS: Transient transfection technology was used to enhance the expression of miR-126 in bone marrow mesenchymal stem cells. Expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 mRNA were detected by real-time PCR, and expression levels of ERK1/2, AKT, pERK1/2, pAKT protein were measured by western blot assay. Forty-eight Sprague-Dawley rats were randomly divided into three groups (n=16 per group), followed by preparation of abdominal free flap models. Rats in the three groups were given injection of miR-126 mimics-transfected cells, miR-126 mimics control-transfected cells and PBS 1 cm and 3 cm distal to the free flap, respectively.
RESULTS AND CONCLUSION: Expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 mRNA in the cells transfected with miR-126 mimics were decreased by 36, 3.5 and 14 times compared with those in the PBS group, respectively. Expressions levels of ERK1/2, AKT, pERK1/2, pAKT protein in the distal free flap increased significantly in the miR-126 mimics group than the other two groups, as did the ratios of pAKT/AKT and pERK1/2/ERK1/2. In addition, the expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 protein in the flap tissue fluid were significantly lower in the miR-126 mimics transfection group than the other two group. All these findings suggest that miR-126 can promote free flap survival by creating favorable conditions for angiogenesis in the free flap tissue.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Surgical Flaps, Transfection, Tissue Engineering

CLC Number:

R394.2

Chen Yong, Fan Long-kun. MicroRNA-126 effects on free flap activity by regulating bone marrow mesenchymal stem cells[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(36): 5332-5337.

Figures/Tables 1

References

[1] Reichenberger MA, Heimer S, Schaefer A, et al. Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury. Stem Cell Rev. 2012;8(3): 854-862.
[2] Medinger M, Passweg J. Angiogenesis in myeloproliferative neoplasms, new markers and future directions. Memo. 2014;7:206-210.
[3] Javazon EH, Keswani SG, Badillo AT, et al. Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic mice treated with adult murine bone marrow stromal progenitor cells. Wound Repair Regen. 2007;15(3):350-359.
[4] Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272-284.
[5] Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008; 15(2):261-271.
[6] Louwette S, Van Geet C, Freson K. Regulators of G protein signaling: role in hematopoiesis, megakaryopoiesis and platelet function. J Thromb Haemost. 2012;10(11):2215-2222.
[7] Ozkan O, Co?kunfirat OK, Ozgenta? HE, et al. New experimental flap model in the rat: free flow-through epigastric flap. Microsurgery. 2004;24(6):454-458.
[8] Landry Y, Lê O, Mace KA, et al. Secretion of SDF-1alpha by bone marrow-derived stromal cells enhances skin wound healing of C57BL/6 mice exposed to ionizing radiation. J Cell Mol Med. 2010; 14(6B):1594-1604.
[9] Kemp K, Gordon D, Wraith DC, et al. Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells. Neuropathol Appl Neurobiol. 2011;37(2): 166-178.
[10] Maggini J, Mirkin G, Bognanni I, et al. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One. 2010;5(2):e9252.
[11] Kronsteiner B, Peterbauer-Scherb A, Grillari-Voglauer R, et al. Human mesenchymal stem cells and renal tubular epithelial cells differentially influence monocyte-derived dendritic cell differentiation and maturation. Cell Immunol. 2011;267(1):30-38.
[12] Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008; 8(9):726-736.
[13] Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007;25(10):2648-2659.
[14] Chen L, Tredget EE, Liu C, et al. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One. 2009;4(9): e7119.
[15] Huang S, Lu G, Wu Y, et al. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair. J Dermatol Sci. 2012;66(1):29-36.
[16] Javazon EH, Keswani SG, Badillo AT, et al. Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic mice treated with adult murine bone marrow stromal progenitor cells. Wound Repair Regen. 2007;15(3):350-359.
[17] Chen L, Tredget EE, Wu PY, et al. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. 2008;3(4):e1886.
[18] Sasaki M, Abe R, Fujita Y, et al. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol. 2008;180(4):2581-2587.