2. Academic Validation
  3. Bexarotene regulates zebrafish embryonic development by activating Wnt signaling pathway

Bexarotene regulates zebrafish embryonic development by activating Wnt signaling pathway

  • Life Sci. 2025 Jul 15:373:123664. doi: 10.1016/j.lfs.2025.123664.
Wenwen Zha 1,  Ziang Wang 1,  Weitao Hu 2,  Chenkai Ge 2,  Wenbin Yuan 2,  Qinyuan Shen 2,  Weirong Li 2,  Wanqing Chen 2,  Jingrong Tang 2,  Zhonghao Xiao 2,  Yunlong Meng 3,  Lirong Huang 3,  Zilin Zhong 3,  Tao-Sheng Li 4,  Jianjun Chen 5,  Zigang Cao 6
Affiliations

Affiliations

  • 1 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, College of Chinese Medicine, Jinggangshan University, Ji'an 343009, China.
  • 2 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Development Biology of Organs and Epigenetics, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, China.
  • 3 Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China.
  • 4 Department of Stem Cell Biology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
  • 5 Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China. Electronic address: chenjianjun@tongji.edu.cn.
  • 6 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Development Biology of Organs and Epigenetics, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, China. Electronic address: 9920160038@jgsu.edu.cn.
PMID: 40288573 DOI: 10.1016/j.lfs.2025.123664
Abstract

Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases.

Keywords

Bexarotene; Embryonic development; Wnt signaling pathway; Zebrafish.

Figures
Products