Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypesopen access
- Authors
- Kim, Hyunbum; Jeong, Ji Hoon; Fendereski, Mona; Lee, Hyo-Shin; Kang, Da Yeon; Hur, Sung Sik; Amirian, Jhaleh; Kim, Yunhye; Pham, Nghia Thi; Suh, Nayoung; Hwang, Nathaniel Suk-Yeon; Ryu, Seongho; Yoon, Jeong Kyo; Hwang, Yongsung
- Issue Date
- Mar-2021
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- synthetic mimic of heparin; poly(sodium-4-styrenesulfonate); myoblast; myogenic differentiation; fusion; focal adhesion kinase (FAK)
- Citation
- International Journal of Molecular Sciences, v.22, no.5
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 22
- Number
- 5
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/19894
- DOI
- 10.3390/ijms22052488
- ISSN
- 1661-6596
1422-0067
- Abstract
- The cell-cell/cell-matrix interactions between myoblasts and their extracellular microenvironment have been shown to play a crucial role in the regulation of in vitro myogenic differentiation and in vivo skeletal muscle regeneration. In this study, by harnessing the heparin-mimicking polymer, poly(sodium-4-styrenesulfonate) (PSS), which has a negatively charged surface, we engineered an in vitro cell culture platform for the purpose of recapitulating in vivo muscle atrophy-like phenotypes. Our initial findings showed that heparin-mimicking moieties inhibited the fusion of mononucleated myoblasts into multinucleated myotubes, as indicated by the decreased gene and protein expression levels of myogenic factors, myotube fusion-related markers, and focal adhesion kinase (FAK). We further elucidated the underlying molecular mechanism via transcriptome analyses, observing that the insulin/PI3K/mTOR and Wnt signaling pathways were significantly downregulated by heparin-mimicking moieties through the inhibition of FAK/Cav3. Taken together, the easy-to-adapt heparin-mimicking polymer-based in vitro cell culture platform could be an attractive platform for potential applications in drug screening, providing clear readouts of changes in insulin/PI3K/mTOR and Wnt signaling pathways.
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- Appears in
Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
- College of Medicine > Department of Pathology > 1. Journal Articles
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