TY - JOUR
T1 - Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes
AU - Kim, Hyunbum
AU - Jeong, Ji Hoon
AU - Fendereski, Mona
AU - Lee, Hyo Shin
AU - Kang, Da Yeon
AU - Hur, Sung Sik
AU - Amirian, Jhaleh
AU - Kim, Yunhye
AU - Pham, Nghia Thi
AU - Suh, Nayoung
AU - Hwang, Nathaniel Suk Yeon
AU - Ryu, Seongho
AU - Yoon, Jeong Kyo
AU - Hwang, Yongsung
N1 - Funding Information:
Funding: This research was supported by a Global Research Development Program grant (2016K1A4-A3914725), a research grant (2020R1A2C1013652), Brain Pool Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2019H1D3A2A02102074), and a research grant (HI17C1193) from the Korea Health Industry Development Institute (KHIDI).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3
Y1 - 2021/3
N2 - The cell–cell/cell–matrix interactions between myoblasts and their extracellular microenvi-ronment 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, observ-ing 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.
AB - The cell–cell/cell–matrix interactions between myoblasts and their extracellular microenvi-ronment 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, observ-ing 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.
KW - Focal adhesion kinase (FAK)
KW - Fusion
KW - Myoblast
KW - Myogenic differ-entiation
KW - Poly(sodium-4-styrenesulfonate)
KW - Synthetic mimic of heparin
UR - https://www.scopus.com/pages/publications/85101688792
U2 - 10.3390/ijms22052488
DO - 10.3390/ijms22052488
M3 - Article
C2 - 33801235
AN - SCOPUS:85101688792
SN - 1661-6596
VL - 22
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 5
M1 - 2488
ER -