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Int J Biol Sci 2023; 19(15):4967-4988. doi:10.7150/ijbs.87332 This issue Cite

Research Paper

Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks

Kexin Jia1, Yinhao Zhang1, Ranyi Luo1, Runping Liu2, Yajing Li1, Jianzhi Wu1, Kaihong Xie1, Jia Liu1, Shuo Li2, Fei Zhou1, Xiaojiaoyang Li1,✉

1. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
2. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.

✉ Corresponding author: Xiaojiaoyang Li, Ph.D. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China. Email: xiaojiaoyang.liedu.cn.

Citation:
Jia K, Zhang Y, Luo R, Liu R, Li Y, Wu J, Xie K, Liu J, Li S, Zhou F, Li X. Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. Int J Biol Sci 2023; 19(15):4967-4988. doi:10.7150/ijbs.87332. https://www.ijbs.com/v19p4967.htm
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Abstract

Graphic abstract

Hepatic ischemia-reperfusion injury (HIRI), a common two-phase intersocietal reaction in liver surgery, typically leading to sustained liver dysfunction. During this process, liver sinusoidal endothelial cells (LSECs) are vulnerable to damage and exert senescence-associated secretory phenotype (SASP). However, how these SASP-LSECs secreted damage-associated molecular patterns (DAMPs) to impact the whole HIRI microenvironment and whether it can be reversed by therapeutics remains unknown. Here, we found that either HIRI surgery or hypoxia and reoxygenation (HR) stimulation forced LSECs into SASP and expressed HMGB1-dominated DAMPs, which were dramatically improved by acteoside (ACT). Additionally, hypoxic hepatocytes released excessive HMGB1 to LSECs and synergistically aggravated their SASP state. Mechanistically, HMGB1 bound with TLR3/TLR4 on LSECs, promoted the nuclear translocation of IRF1 and subsequent transcription of cxcl1 and Hmgb1, leading to the chemotaxis of neutrophils and accelerating immune damage in a vicious circle. Notably, ACT or HMGB1 siRNA effectively disrupted HMGB1-TLR3/4 interaction, leading to IRF1 inhibition and repairing LSEC functions, which was largely reversed by HMGB1 stimulation and IRF1-overexpressed liposomes with LSECs-targeted hyaluronic acid-derivative conjugated in mice. Collectively, ACT reversed the senescent fate of LSECs and restored sinusoidal networks by targeting HMGB1-TLR3/4-IRF1 signaling, thus providing protection against HIRI and offering the potential for new therapeutics development.

Keywords: hepatic ischemia-reperfusion injury, liver sinusoidal endothelial cell, senescence-associated secretory phenotype, acteoside, high mobility group protein 1.

Citation styles

APA
Jia, K., Zhang, Y., Luo, R., Liu, R., Li, Y., Wu, J., Xie, K., Liu, J., Li, S., Zhou, F., Li, X. (2023). Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. International Journal of Biological Sciences, 19(15), 4967-4988. https://doi.org/10.7150/ijbs.87332.

ACS
Jia, K.; Zhang, Y.; Luo, R.; Liu, R.; Li, Y.; Wu, J.; Xie, K.; Liu, J.; Li, S.; Zhou, F.; Li, X. Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. Int. J. Biol. Sci. 2023, 19 (15), 4967-4988. DOI: 10.7150/ijbs.87332.

NLM
Jia K, Zhang Y, Luo R, Liu R, Li Y, Wu J, Xie K, Liu J, Li S, Zhou F, Li X. Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. Int J Biol Sci 2023; 19(15):4967-4988. doi:10.7150/ijbs.87332. https://www.ijbs.com/v19p4967.htm

CSE
Jia K, Zhang Y, Luo R, Liu R, Li Y, Wu J, Xie K, Liu J, Li S, Zhou F, Li X. 2023. Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. Int J Biol Sci. 19(15):4967-4988.

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