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Int. J. Mol. Sci. 2017, 18(9), 1917; doi:10.3390/ijms18091917

Dual Role of MiR-21-Mediated Signaling in HUVECs and Rat Surgical Flap under Normoxia and Hypoxia Condition

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Division of Plastic and Reconstructive Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Author to whom correspondence should be addressed.
Received: 7 August 2017 / Revised: 1 September 2017 / Accepted: 4 September 2017 / Published: 7 September 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Restoring sufficient vascularity of the ischemia/hypoxia flap is always the critical issue in flap surgeries. In a previous studies microRNA-21 (miR-21) expression was upregulated after rat skin flap surgery. MiR-21 has been reported to be induced by hypoxia and the function of miR-21 involves in the process of angiogenesis. However, the precise regulatory mechanisms in miR-21-mediated pathways are still unclear. These issues were investigated via in vitro and in vivo experiments in this study. In human umbilical vein endothelial cells (HUVEC), the expression of hsa-miR-21-5p was induced after hypoxic culture and the induction of hsa-miR-21-5p was suppressed after sequential normoxic culture. Moreover, transfection of hsa-miR-21-5p mimic enhanced tube formation capacity in normoxia, but attenuated it in hypoxia. Furthermore, bioinformatic analysis suggested that SMAD7 was a predicted target of hsa-miR-21-5p. Our results demonstrated the effect of hsa-miR-21-5p was different on SMAD7 expression in normoxia and hypoxia. In rat skin flaps, blockage of miR-21-5p significantly increased angiogenesis via analysis of color laser Doppler imaging and repressed SMAD7 expression in ischemic skin tissue. Our study showed the opposite effect of miR-21-5p mediating angiogenesis in normoxia and hypoxia, providing important implications regarding the design of novel miRNA-based therapeutic strategies in flap surgeries. View Full-Text
Keywords: hypoxia; angiogenesis; MicroRNA-21 (miR-21); SMAD7 hypoxia; angiogenesis; MicroRNA-21 (miR-21); SMAD7

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chang, C.-H.; Yen, M.-C.; Liao, S.-H.; Hsu, Y.-L.; Lai, C.-S.; Kuo, Y.-R.; Hsu, Y.-L. Dual Role of MiR-21-Mediated Signaling in HUVECs and Rat Surgical Flap under Normoxia and Hypoxia Condition. Int. J. Mol. Sci. 2017, 18, 1917.

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