Abstract
Cell–substrate interaction is important in tissue engineering. Vascular smooth muscle cells (VSMCs) cultured on the microgrooved surface of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) showed a distinctive polarized morphology and a high expression level of let-7a compared with the flat substrates. LIMK2, a crucial regulator of actin dynamics, was identified as a new target of let-7a. F-Actin content on flat substrates was significantly higher than that on microgrooved ones. Either overexpression of let-7a on flat substrates or inhibited expression on microgrooved substrates can rescue the difference. In accord with actin dynamics, the expressions of contractile smooth muscle markers, such as SM22 and SMA, decreased in VSMCs cultured on microgrooved substrates compared to those on flat ones, though PHBHHx can induce the synthetic-to-contractile phenotype shift. These results indicate that microgrooved PHBHHx could enhance actin dynamics of VSMCs through let-7a-involved regulation and trigger a synthetic shift.
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Acknowledgments
The authors would like to thank Prof. Jianzhong Xi in College of Engineering, Peking University for donating modified pGL3 plasmid. This research was supported by Natural Sciences Foundation of China (Grant No. 31170940), National High Technology Research and Development (863 Program) (Grant No. 2012AA020503, 2013AA020301 and 2012AA02A700), 973 Basic Research Fund (Grant No. 2012CB725204) and Tsinghua University Initiative Scientific Research Program (No. 20131089199).
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Yan Li and Wen Shao are co-first authors.
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Li, Y., Shao, W., Jin, S. et al. Microgrooved poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) affects the phenotype of vascular smooth muscle cells through let-7a-involved regulation of actin dynamics. Biotechnol Lett 36, 2125–2133 (2014). https://doi.org/10.1007/s10529-014-1562-x
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DOI: https://doi.org/10.1007/s10529-014-1562-x