CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2023-03-13
Cited: 0
Clicked: 1454
Citations: Bibtex RefMan EndNote GB/T7714
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.
[1]BernsmeierC, van der MerweS, PérianinA, 2020. Innate immune cells in cirrhosis. J Hepatol, 73(1):186-201.
[2]CaiXP, CaiHQ, WangJ, et al., 2022. Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(4):265-285.
[3]ChenLS, YaoXW, YaoHB, et al., 2020. Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J, 34(4):5178-5192.
[4]DingN, YuRT, SubramaniamN, et al., 2013. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell, 153(3):601-613.
[5]DongBN, ZhouY, WangW, et al., 2020. Vitamin D receptor activation in liver macrophages ameliorates hepatic inflammation, steatosis, and insulin resistance in mice. Hepatology, 71(5):1559-1574.
[6]DuranA, HernandezED, Reina-CamposM, et al., 2016. P62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell, 30(4):595-609.
[7]HuMY, WangY, LiuZS, et al., 2021. Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis. Nat Nanotechnol, 16(4):466-477.
[8]KalluriR, LeBleuVS, 2020. The biology, function, and biomedical applications of exosomes. Science, 367(6478):eaau6977. http://doi.org/10.1126/science.aau6977
[9]KisselevaT, BrennerD, 2021. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol, 18(3):151-166.
[10]KonstantakisC, TselekouniP, KalafateliM, et al., 2016. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol, 29(3):297-306.
[11]LiPF, MaC, LiJ, et al., 2022. Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(5):407-422.
[12]LiuPT, StengerS, LiHY, et al., 2006. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 311(5768):1770-1773.
[13]LuZN, NiuWX, ZhangN, et al., 2021. Pantoprazole ameliorates liver fibrosis and suppresses hepatic stellate cell activation in bile duct ligation rats by promoting YAP degradation. Acta Pharmacol Sin, 42(11):1808-1820.
[14]MokdadAA, LopezAD, ShahrazS, et al., 2014. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med, 12:145.
[15]PellicoroA, RamachandranP, IredaleJP, et al., 2014. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol, 14(3):181-194.
[16]QuC, ZhengDD, LiS, et al., 2018. Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis. Hepatology, 68(3):1125-1139.
[17]RanY, XiongMG, XuZS, et al., 2019. YIPF5 is essential for innate immunity to DNA virus and facilitates COPII-dependent STING trafficking. J Immunol, 203(6):1560-1570.
[18]SassiF, TamoneC, D'AmelioP, 2018. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients, 10(11):1656.
[19]SekiE, SchwabeRF, 2015. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology, 61(3):1066-1079.
[20]ShenDF, ChengH, CaiBZ, et al., 2022. N-n-Butyl haloperidol iodide ameliorates liver fibrosis and hepatic stellate cell activation in mice. Acta Pharmacol Sin, 43(1):133-145.
[21]ShenZR, ShaoJJ, SunJQ, et al., 2022. Exosomes released by melanocytes modulate fibroblasts to promote keloid formation: a pilot study. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(8):699-704.
[22]SicaA, InvernizziP, MantovaniA, 2014. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology, 59(5):2034-2042.
[23]SoonthornsitJ, SakaiN, SasakiY, et al., 2017. YIPF1, YIPF2, and YIPF6 are medial-/trans-Golgi and trans-Golgi network-localized Yip domain family proteins, which play a role in the Golgi reassembly and glycan synthesis. Exp Cell Res, 353(2):100-108.
[24]StolleK, SchnoorM, FuellenG, et al., 2005. Cloning, cellular localization, genomic organization, and tissue-specific expression of the TGFβ1-inducible SMAP-5 gene. Gene, 351:119-130.
[25]SunYY, LiXF, MengXM, et al., 2017. Macrophage phenotype in liver injury and repair. Scand J Immunol, 85(3):166-174.
[26]TaguchiY, HoriuchiY, KanoF, et al., 2017. Novel prosurvival function of Yip1A in human cervical cancer cells: constitutive activation of the IRE1 and PERK pathways of the unfolded protein response. Cell Death Dis, 8(3):e2718.
[27]TheryC, WitwerKW, AikawaE, et al., 2018. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles, 7(1):1535750. http://doi.org/10.1080/20013078.2018.1535750
[28]TsuchidaT, FriedmanSL, 2017. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol, 14(7):397-411.
[29]WangKW, 2015. Autophagy and apoptosis in liver injury. Cell Cycle, 14(11):1631-1642.
[30]WangXP, WangGY, QuJW, et al., 2020. Calcipotriol inhibits NLRP3 signal through YAP1 activation to alleviate cholestatic liver injury and fibrosis. Front Pharmacol, 11:200.
[31]WangZL, YangJJ, SunXH, et al., 2023. Exosome-mediated regulatory mechanisms in skeletal muscle: a narrative review. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 24(1):1-14.
[32]YinCY, EvasonKJ, AsahinaK, et al., 2013. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest, 123(5):1902-1910.
[33]ZhouY, DongBN, KimKH, et al., 2020. Vitamin D receptor activation in liver macrophages protects against hepatic endoplasmic reticulum stress in mice. Hepatology, 71(4):1453-1466.
Open peer comments: Debate/Discuss/Question/Opinion
<1>