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On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2023-03-13

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Cong WANG

https://orcid.org/0000-0001-8241-807X

Can ZHANG

https://orcid.org/0000-0003-3529-5438

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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.3 P.248-261

http://doi.org/10.1631/jzus.B2200383


Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5)


Author(s):  Xuwentai LIU, Yue WU, Yanyi LI, Kaiming LI, Siyuan HOU, Ming DING, Jingmin TAN, Zijing ZHU, Yingqi TANG, Yuming LIU, Qianhui SUN, Cong WANG, Can ZHANG

Affiliation(s):  State Key Laboratory of Natural Medicines / Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases / Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, China

Corresponding email(s):   zhangcan@cpu.edu.cn, wangcong@cpu.edu.cn

Key Words:  Hepatic fibrosis, Hepatic stellate cell (HSC), Macrophage, Exosome, Vitamin D receptor (VDR), Smooth muscle cell-associated protein 5 (SMAP-5)


Xuwentai LIU, Yue WU, Yanyi LI, Kaiming LI, Siyuan HOU, Ming DING, Jingmin TAN, Zijing ZHU, Yingqi TANG, Yuming LIU, Qianhui SUN, Cong WANG, Can ZHANG. Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5)[J]. Journal of Zhejiang University Science B, 2023, 24(3): 248-261.

@article{title="Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5)",
author="Xuwentai LIU, Yue WU, Yanyi LI, Kaiming LI, Siyuan HOU, Ming DING, Jingmin TAN, Zijing ZHU, Yingqi TANG, Yuming LIU, Qianhui SUN, Cong WANG, Can ZHANG",
journal="Journal of Zhejiang University Science B",
volume="24",
number="3",
pages="248-261",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200383"
}

%0 Journal Article
%T Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5)
%A Xuwentai LIU
%A Yue WU
%A Yanyi LI
%A Kaiming LI
%A Siyuan HOU
%A Ming DING
%A Jingmin TAN
%A Zijing ZHU
%A Yingqi TANG
%A Yuming LIU
%A Qianhui SUN
%A Cong WANG
%A Can ZHANG
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 3
%P 248-261
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200383

TY - JOUR
T1 - Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5)
A1 - Xuwentai LIU
A1 - Yue WU
A1 - Yanyi LI
A1 - Kaiming LI
A1 - Siyuan HOU
A1 - Ming DING
A1 - Jingmin TAN
A1 - Zijing ZHU
A1 - Yingqi TANG
A1 - Yuming LIU
A1 - Qianhui SUN
A1 - Cong WANG
A1 - Can ZHANG
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 3
SP - 248
EP - 261
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200383


Abstract: 
An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.

维生素D受体(VDR)通过调节M2巨噬细胞外泌体SMAP-5介导肝星状细胞的静息

刘许文泰, 吴越, 李彦懿, 李凯明, 侯思源, 丁明, 谈敬敏, 祝子婧, 汤迎琦, 刘煜明, 孙千惠, 王聪, 张灿
中国药科大学高端药物制剂与材料研究中心, 江苏省代谢性疾病药物重点实验室, "天然药物活性组分与药效"国家重点实验室, 中国南京市, 210009
概要: 肝纤维化有效治疗方案的制定需要深入了解其发病机制。肝纤维化的特征是活化的肝星状细胞(aHSC)过度产生细胞外基质。尽管已证实M2巨噬细胞能促进HSC活化,但所涉及的分子机制仍不明确。在此,我们提出参与巨噬细胞极化的维生素D受体(VDR)可能通过改变巨噬细胞外泌体的功能来调节巨噬细胞和HSC之间的通信。本研究证实,激动VDR可以抑制M2巨噬细胞对HSC活化的促进作用。源自M2巨噬细胞的外泌体可以促进HSC活化,同时激动VDR改变了M2外泌体中的蛋白质组分并逆转其激活HSC的作用。平滑肌细胞相关蛋白5(SMAP-5)被发现是M2巨噬细胞外泌体促进HSC活化的关键效应蛋白,其作用机制是通过调节HSC的自噬通量。基于这些结果表明,VDR激动剂和巨噬细胞外泌体分泌抑制剂的联合治疗可获得更加优异的抗肝纤维化效果。本研究旨在阐明VDR和巨噬细胞在HSC激活中的关联,其结果有助于对肝纤维化的发病机制理解,并为肝纤维化的治疗提供潜在的靶点。

关键词:肝纤维化;肝星状细胞(HSC);巨噬细胞;外泌体;维生素D受体(VDR);平滑肌细胞相关蛋白5(SMAP-5)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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