2. Academic Validation
  3. Simetryn induces arteriovenous malformations in zebrafish embryos through activation of Erk signaling

Simetryn induces arteriovenous malformations in zebrafish embryos through activation of Erk signaling

  • Biochem Biophys Res Commun. 2026 Mar 12:804:153339. doi: 10.1016/j.bbrc.2026.153339.
Zhonghao Xiao 1,  Daoyu Wu 1,  Chenglong Duan 1,  Ji Zhang 2,  Weitao Hu 1,  Jingrong Tang 1,  Ziang Wang 1,  Huimin Li 1,  Xiaowen Shi 1,  Sizhou Huang 3,  Zigang Cao 4
Affiliations

Affiliations

  • 1 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, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China.
  • 2 Department of Clinical Laboratory, Rugao Hospital of Traditional Chinese Medicine, Nantong, 226000, Jiangsu, China.
  • 3 Aging Research Key Laboratory of Sichuan Province, Key Laboratory of Thermoregulation and Inflammation at Chengdu Medical College of Sichuan Province, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, 610500, China; Department of Neurology, the Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610000, China.
  • 4 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, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China. Electronic address: [email protected].
PMID: 41619513 DOI: 10.1016/j.bbrc.2026.153339
Abstract

Arteriovenous malformations (AVMs) represent a congenital, high-flow vascular anomaly characterized by direct, aberrant connections between arteries and veins. This pathology leads to diverse clinical manifestations including skin discoloration, pain, ulceration, hemorrhage, and disfigurement. While most current animal AVM models rely on genetic engineering, chemically induced models remain scarce. In this study, we report that simetryn, a triazine Herbicide, can induce AVM-like phenotypes in zebrafish embryos. Exposure to simetryn caused aberrant vascular development and erythrocyte accumulation within the caudal vascular plexus. We also observed a reduction in caudal lymphatic vessels and disrupted of cerebral vasculature. In the caudal vascular plexus, cellular proliferation was decreased while Apoptosis was increased. Mechanistically, simetryn upregulated levels of phosphorylated ERK (p-Erk),. Notably, these AVM-like phenotypes were ameliorated by co-treatment with trametinib, a MEK Inhibitor acting upstream of ERK. Our findings establish a novel, drug-induced zebrafish model of AVMs, which holds promise for facilitating high-throughput drug screening and advance the study of AVM pathogenesis.

Keywords

Arteriovenous malformation; Blood vessels; P-Erk; Simetryn; Zebrafish.

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