Emerging role of Jumonji domain-containing protein D3 (JMJD3) in inflammatory diseases

Xiang Li; Ru-Yi Chen; Jin-Jin Shi; Chang-Yun Li; Yan-Jun Liu; Chang Gao; Ming-Rong Gao; Shun Zhang; Jian-Fei Lu; Jia-Feng Cao; Guan-Jun Yang; Jiong Chen

doi:10.1016/j.jpha.2024.100978

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2024 > Accepted Manu

Xiang Li, Ru-Yi Chen, Jin-Jin Shi, Chang-Yun Li, Yan-Jun Liu, Chang Gao, Ming-Rong Gao, Shun Zhang, Jian-Fei Lu, Jia-Feng Cao, Guan-Jun Yang, Jiong Chen. Emerging role of Jumonji domain-containing protein D3 (JMJD3) in inflammatory diseases[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100978

Citation:

Xiang Li, Ru-Yi Chen, Jin-Jin Shi, Chang-Yun Li, Yan-Jun Liu, Chang Gao, Ming-Rong Gao, Shun Zhang, Jian-Fei Lu, Jia-Feng Cao, Guan-Jun Yang, Jiong Chen. Emerging role of Jumonji domain-containing protein D3 (JMJD3) in inflammatory diseases[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100978

Citation:

Xiang Li, Ru-Yi Chen, Jin-Jin Shi, Chang-Yun Li, Yan-Jun Liu, Chang Gao, Ming-Rong Gao, Shun Zhang, Jian-Fei Lu, Jia-Feng Cao, Guan-Jun Yang, Jiong Chen. Emerging role of Jumonji domain-containing protein D3 (JMJD3) in inflammatory diseases[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100978

PDF( 18301 KB)

Emerging role of Jumonji domain-containing protein D3 (JMJD3) in inflammatory diseases

doi: 10.1016/j.jpha.2024.100978

Xiang Li^a,b,
Ru-Yi Chen^a,b,
Jin-Jin Shi^a,b,
Chang-Yun Li^a,b,
Yan-Jun Liu^a,b,
Chang Gao^a,b,
Ming-Rong Gao^a,b,
Shun Zhang^c,d,
Jian-Fei Lu^a,b,
Jia-Feng Cao^a,b,
Guan-Jun Yang^{a,b
,
,},
Jiong Chen^{a,b
,}

a State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang, 315211, China;
b Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang, 315211, China;
c Ningbo No. 2 Hospital, Ningbo, Zhejiang, 315211, China;
d China Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, 315211, China

Funds:

This work is supported by the Natural Science Foundation of Zhejiang Province, China (Grant No.: LY24C190001), the General Scientific Research Project of Education of Zhejiang Province, China (Grant Nos.: Y202352559 and Y202147351), the Starting Research Fund of Ningbo University, China (Grant No.: 421912073), and the Student Research and Innovation Program of Ningbo University, China (Grant Nos.: 2023SRIP1810 and 2023SRIP1804).

Received Date: Dec. 18, 2023
Rev Recd Date: Apr. 10, 2024
Available Online: Apr. 19, 2024

Abstract

Abstract

Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri- 6 methylated groups from lysine 27 on histone (H3K27me2/3). The erasure of these 7 marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3’s role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.
- JMJD3,
- Inflammation,
- Histone demethylation,
- Inhibitor

FullText(HTML)

References(41)

References

[1]	Y.-J. Liu, H. Wang, H.-J. Zhong, et al., Editorial:Epigenetics of the immune 917 component of inflammation, Front. Immunol. 13(2022), 1000836.
[2]	Y.-J. Liu, H.-J. Zhong, H. Wang, et al., Editorial:Community series in epigenetics of 919 the immune component of inflammation-volume II, Front. Immunol. 14(2023), 9201266133.
[3]	Y.M.D. Lo, D.S.C. Han, P. Jiang, et al., Epigenetics, fragmentomics, and topology of 922 cell-free DNA in liquid biopsies, Science 372(2021), eaaw3616.
[4]	G.-J. Yang, J. Wu, L. Miao, et al., Pharmacological inhibition of KDM5A for cancer 924 treatment, Eur. J. Med. Chem. 226(2021), 113855.
[5]	A. Salminen, K. Kaarniranta, M. Hiltunen, et al., Histone demethylase Jumonji D3926(JMJD3/KDM6B) at the nexus of epigenetic regulation of inflammation and the 927 aging process, J. Mol. Med.(Berl). 92(2014)1035-1043.
[6]	X. Zhang, L. Liu, X. Yuan, et al., JMJD3 in the regulation of human diseases, Protein 929 Cell 10(2019)864-882.
[7]	T. Swigut, J. Wysocka, H3K27 demethylases, at long last, Cell 131(2007)29-32.
[8]	L.-J. Chen, X.-Y. Xu, X.-D. Zhong, et al., The role of lysine-specific demethylase 6A 932(KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy, Bioorg. 933 Chem. 133(2023), 106409.
[9]	N.T. Ashley, Z.M. Weil, R.J. Nelson, Inflammation:Mechanisms, costs, and natural 935 variation, Annu. Rev. Ecol. Evol. S. 43(2012)385-406. 936 https://doi.org/10.1146/annurev-ecolsys-040212-092530.
[10]	C. Nathan, A. Ding, Nonresolving inflammation, Cell 140(2010)871-882.
[11]	Y. Ding, Y. Yao, X. Gong, et al., JMJD3:A critical epigenetic regulator in stem cell 939 fate, Cell Commun. Signal. 19(2021), 72.
[12]	F. De Santa, M.G. Totaro, E. Prosperini, et al., The histone H3 lysine-27941 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene 942 silencing, Cell 130(2007)1083-1094.
[13]	K.M. Arcipowski, C.A. Martinez, P. Ntziachristos, Histone demethylases in 944 physiology and cancer:A tale of two enzymes, JMJD3 and UTX, Curr. Opin. 945 Genet. Dev. 36(2016)59-67.
[14]	P.D. Hsu, E.S. Lander, F. Zhang, Development and applications of CRISPR-Cas9 for 947 genome engineering, Cell 157(2014)1262-1278.
[15]	R.J. Klose, E.M. Kallin, Y. Zhang, JmjC-domain-containing proteins and histone 949 demethylation, Nat. Rev. Genet. 7(2006)715-727.
[16]	S. Hong, Y.-W. Cho, L.-R. Yu, et al., Identification of JmjC domain-containing UTX 951 and JMJD3 as histone H3 lysine 27 demethylases, Proc. Natl. Acad. Sci. USA 104952(2007)18439-18444.
[17]	L.R F. A, KDM6B (JMJD3) and its dual role in cancer, Biochimie 184(2021)63-71.
[18]	L. Kruidenier, C.-W. Chung, Z. Cheng, et al., A selective jumonji H3K27955 demethylase inhibitor modulates the proinflammatory macrophage response, 956 Nature 488(2012)404-408.
[19]	W. Zhao, Q. Li, S. Ayers, et al., Jmjd3 inhibits reprogramming by upregulating 958 expression of INK4a/Arf and targeting PHF20 for ubiquitination, Cell 152(2013)9591037-1050.
[20]	G.-J. Yang, Y.-J. Liu, L.-J. Ding, et al., A state-of-the-art review on LSD1 and its 961 inhibitors in breast cancer:Molecular mechanisms and therapeutic significance, 962 Front. Pharmacol. 13(2022), 989575.
[21]	C.-Y. Li, Y.-J. Liu, F. Tao, et al., Lysine-specific demethylase 7A (KDM7A):A 964 potential target for disease therapy, Biochem. Pharmacol. 216(2023), 115799.
[22]	A. Jakkampudi, R. Jangala, B.R. Reddy, et al., NF-κB in acute pancreatitis:966 Mechanisms and therapeutic potential, Pancreatology 16(2016)477-488.
[23]	I.S. Afonina, Z. Zhong, M. Karin, et al., Limiting inflammation-the negative 968 regulation of NF-κB and the NLRP3 inflammasome, Nat. Immunol. 18(2017)861-969869.
[24]	Y. Wei, R. Chen, S. Dimicoli, et al., Global H3K4me3 genome mapping reveals 971 alterations of innate immunity signaling and overexpression of JMJD3 in human 972 myelodysplastic syndrome CD34+cells, Leukemia 27(2013)2177-2186.
[25]	N.D. Das, K.H. Jung, M.R. Choi, et al., Gene networking and inflammatory pathway 974 analysis in a JMJD3 knockdown human monocytic cell line, Cell Biochem. Funct. 97530(2012)224-232.
[26]	S. Yu, X. Chen, M. Xiu, et al., The regulation of Jmjd3 upon the expression of NF-977κB downstream inflammatory genes in LPS activated vascular endothelial cells, 978 Biochem. Biophys. Res. Commun. 485(2017)62-68.
[27]	Y. Pan, J. Wang, Y. Xue, et al., GSKJ4 protects mice against early sepsis via 980 reducing proinflammatory factors and up-regulating miR-146a, Front. Immunol. 9981(2018), 2272.
[28]	J. Sun, X. Sun, J. Chen, et al., microRNA-27b shuttled by mesenchymal stem cell-983 derived exosomes prevents sepsis by targeting JMJD3 and downregulating NF-κB 984 signaling pathway, Stem Cell Res. Ther. 12(2021), 14.
[29]	J. Zhou, X. Jin, Y. Liu, et al., Jumonji domain containing-3(JMJD3) inhibition 986 attenuates IL-1β-induced chondrocytes damage in vitro and protects osteoarthritis 987 cartilage in vivo, Inflamm. Res. 69(2020)657-666.
[30]	F.M. Davis, L.C. Tsoi, W.J. Melvin, et al., Inhibition of macrophage histone 989 demethylase JMJD3 protects against abdominal aortic aneurysms, J. Exp. Med. 218990(2021), e20201839.
[31]	H. Wu, R. Wang, X. Qin, et al., Effects of chronic stress on depressive-like behaviors 992 and JMJD3 expression in the prefrontal cortex and hippocampus of C57BL/6 and 993 ob/ob mice, J. Psychiatr. Res. 133(2021)142-155.
[32]	R. Wang, W. Wang, J. Xu, et al., Jmjd3 is involved in the susceptibility to depression 995 induced by maternal separation via enhancing the neuroinflammation in the 996 prefrontal cortex and hippocampus of male rats, Exp. Neurol. 328(2020), 113254.
[33]	R. Wang, W. Wang, J. Xu, et al., Dynamic effects of early adolescent stress on 998 depressive-like behaviors and expression of cytokines and JMJD3 in the prefrontal 999 cortex and hippocampus of rats, Front. Psychiatry 9(2018), 471.
[34]	L. Chen, X. Zhang, Y. Liu, et al., JMJD3 is required for acute pancreatitis and 1001 pancreatitis-associated lung injury, J. Immunol. 210(2023)180-190.
[35]	Y. Gao, N. Wang, D. Jia, JMJD3 downregulates IL4i1 aggravating 1003 lipopolysaccharide-induced acute lung injury via H3K27 and H3K4 demethylation, 1004 Environ. Toxicol. 38(2023)754-769.
[36]	P. Przanowski, M. Dabrowski, A. Ellert-Miklaszewska, et al., The signal transducers 1006 Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory 1007 genes in microglia, J. Mol. Med.(Berl). 92(2014)239-254.
[37]	D. Pham, Q. Yu, C.C. Walline, et al., Opposing roles of STAT4 and Dnmt3a in Th11009 gene regulation, J. Immunol. 191(2013)902-911.
[38]	U.-K. Hanisch, Linking STAT and TLR signaling in microglia:A new role for the 1011 histone demethylase Jmjd3, J. Mol. Med.(Berl). 92(2014)197-200.
[39]	R. Song, L. Lin, Glycoprotein nonmetastatic melanoma protein B (GPNMB)1013 ameliorates the inflammatory response in periodontal disease, Inflammation 421014(2019)1170-1178.
[40]	Y. Shentu, Q. Tian, J. Yang, et al., Upregulation of KDM6B contributes to 1016 lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in 1017 mice, Behav. Brain Res. 408(2021), 113305.
[41]	X.-Y. Leng, J. Yang, H. Fan, et al., JMJD3/H3K27me3 epigenetic modification 1019 regulates Th17/Treg cell differentiation in ulcerative colitis, Int. Immunopharmacol. 1020110(2022), 109000.