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World J Gastroenterol. Jan 14, 2027; 33(2): 123795
Published online Jan 14, 2027. doi: 10.3748/wjg.123795
Published online Jan 14, 2027. doi: 10.3748/wjg.123795
Melatonin attenuates splanchnic hyperdynamic circulation in cirrhotic portal hypertension by disrupting POMK-VEGFR2 interaction
Guang-Bo Wu, Gu-Qing Luo, Meng Luo, Hai-Zhong Huo, Qiang Fan, Department of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China
Min Chen, Department of Urology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China
Kua-Wen Cai, Xiao-Tong You, Fu Han, Qing Li, Qiang Fan, Department of General Surgery, The First People’s Hospital of Lancang Lahu Autonomous Country, Pu’er 665600, Yunnan Province, China
Na-Zhu Zhang, Department of Ophthalmology, The First People’s Hospital of Lancang Lahu Autonomous Country, Pu’er 665600, Yunnan Province, China
Co-first authors: Guang-Bo Wu and Gu-Qing Luo.
Co-corresponding authors: Hai-Zhong Huo and Qiang Fan.
Author contributions: Wu GB and Luo GQ wrote the original draft and were responsible for formal analysis as co-first authors; Wu GB, Luo GQ, Chen M, and Fan Q accounted for conceptualisation, methodology, validation, and project administration; Wu GB, Chen M, Li Q and Fan Q contributed to writing-reviewing and editing and visualisation; Chen M and Fan Q were in charge of funding acquisition; Cai KW, You XT, Han F and Zhang NZ were responsible for software and data curation; Luo M, Huo HZ, and Fan Q were in charge of supervision; Huo HZ and Fan Q have played important and indispensable roles in the experimental design as co-corresponding authors; all authors read and approved of the final manuscript.
AI contribution statement: AI tools were not used during manuscript preparation.
Supported by National Natural Science Foundation of China, No. 82500736 and No. 81970526; China Postdoctoral Science Foundation General Fund, No. 2025M771961; Yunnan Province Science and Technology Plan Project Medical and Health Special Project, No. 202603CL100029; and Pu’er Municipal Science and Technology Bureau of Yunnan Province, Key Project of the Joint Special Program for Medical Research, No. KJXM202509080389.
Institutional animal care and use committee statement: This study was approved by the Ethical Committee of Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, No. SH9H-2019-A201-1.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data in the current study are available from the corresponding author upon reasonable request.
Corresponding author: Qiang Fan, MD, Department of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, No. 639 Manufacturing Bureau Road, Shanghai 200011, China. 13472665251@163.com
Received: May 29, 2026
Revised: July 30, 2026
Accepted: September 24, 2026
Published online: January 14, 2027
Processing time: 163 Days and 6.2 Hours
Revised: July 30, 2026
Accepted: September 24, 2026
Published online: January 14, 2027
Processing time: 163 Days and 6.2 Hours
Core Tip
Core Tip: This study uncovers a novel protective role for melatonin (MLT) in alleviating splanchnic hyperdynamic circulation in cirrhotic portal hypertension. Using in vivo and in vitro models, we demonstrate that MLT effectively reduces portal pressure by inhibiting pathological mesenteric angiogenesis. Mechanistically, our multi-omics and functional analyses reveal for the first time that MLT exerts its anti-angiogenic effects by specifically disrupting the physical interaction between POMK and VEGFR-2, thereby dampening the VEGF signaling cascade. These findings highlight the POMK-VEGFR-2 axis as a critical pathophysiological driver and propose MLT as a promising, translatable candidate for managing cirrhotic hemodynamic complications.