Trolox-induced cardiac differentiation is mediated by the inhibition of Wnt/β-catenin signaling in human embryonic stem cells

Mu Seog Choe; Han Cheol Yeo; Chang Min Bae; Ho Jae Han; Kyung Min Baek; Joong Sun Kim; Kyung Seob Lim; In-Sik Shin; Woochul Chang; Seung Pil Yun; Ho Jin Lee; Min Young Lee

doi:10.1002/cbin.11200

Trolox-induced cardiac differentiation is mediated by the inhibition of Wnt/β-catenin signaling in human embryonic stem cells

Cell Biol Int. 2019 Dec;43(12):1505-1515. doi: 10.1002/cbin.11200. Epub 2019 Jul 23.

Authors

Affiliations

¹ Department of Molecular Pharmacology, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Daegu, 41566, Korea.
² Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Seoul, 08826, Korea.
³ Department of Cardiovascular and Neurologic Disease, College of Oriental Medicine, Daegu Haany University, 136 Sincheondong-ro, Daegu, 42158, Korea.
⁴ Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111 Geonjae-ro, Naju, Jeollanam-do 58245, Korea.
⁵ Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Cheongju, Chungcheongbuk-do 28116, Korea.
⁶ Department of Veterinary Pharmacology, College of Veterinary Medicine (BK21 Project Team), Chonnam National University, 77 Yongbong-ro, Gwangju, 61186, Korea.
⁷ Department of Biology Education, College of Education, Pusan National University, 2 Busandaehak-ro, Busan, 46241, Korea.
⁸ Department of Pharmacology, School of Medicine, Gyeongsang National University, 15 Jinjudae-ro 816, Jinju, 52727, Korea.
⁹ Department of Pharmacology, School of Medicine, Yale University, 333 Cedar street, New Haven, Connecticut, 06520, USA.

PMID: 31293030
DOI: 10.1002/cbin.11200

Abstract

Cardiac differentiation of human pluripotent stem cells may be induced under chemically defined conditions, wherein the regulation of Wnt/β-catenin pathway is often desirable. Here, we examined the effect of trolox, a vitamin E analog, on the cardiac differentiation of human embryonic stem cells (hESCs). 6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox) significantly enhanced cardiac differentiation in a time- and dose-dependent manner after the mesodermal differentiation of hESCs. Trolox promoted hESC cardiac differentiation through its inhibitory activity against the Wnt/β-catenin pathway. This study demonstrates an efficient cardiac differentiation method and reveals a novel Wnt/β-catenin regulator.

Keywords: cardiac differentiation; human embryonic stem cells; trolox.

Grants and funding

NRF-2018R1D1A1A02044017/Korean government