title: Microgrooved poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) affects the phenotype of vascular smooth muscle cells through let-7a-involved regulation of actin dynamics.
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.
authors: MOE Key Laboratory of Bioinformatics and Center for Epigenetics and Chromatin, School of Life Sciences, Tsinghua University, Beijing, 100084, People's Republic of China, liyan@973pha.org.
authors: Yan
authors: Y
authors: Li
authors: Wen
authors: W
authors: Shao
authors: Shouhong
authors: S
authors: Jin
authors: Tuan
authors: T
authors: Xu
authors: Xianli
authors: X
authors: Jiang
authors: Shihchi
authors: S
authors: Yang
authors: Zheyao
authors: Z
authors: Wang
authors: Junbiao
authors: J
authors: Dai
authors: Qiong
authors: Q
authors: Wu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D001672:Biocompatible Materials / Q000737:chemistry*; D002208:Caproates / Q000737:chemistry*; D018929:Cell Culture Techniques; D002460:Cell Line; D005786:Gene Expression Regulation; D054461:Lim Kinases / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D002208:Caproates; D035683:MicroRNAs; C542687:mirnlet7 microRNA, mouse; C045051:3-hydroxyhexanoic acid; D054461:Lim Kinases; C095325:Limk2 protein, mouse; D020155:3-Hydroxybutyric Acid