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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

1
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Division of Plastic and Reconstructive Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3
Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4
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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Abstract

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
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MDPI and ACS Style

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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