Role of the PADI Family in Inflammatory Autoimmune Diseases and Cancers: A Systematic Review

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 6

PMID 37020554

Authors

Changhui Zhu

Chunyan Liu

Zhengbin Chai

Affiliations

Soon will be listed here.

Abstract

The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.

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References

Engstrom M, Eriksson K, Lee L, Hermansson M, Johansson A, Nicholas A . Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis. J Transl Med. 2018; 16(1):214. PMC: 6069803. DOI: 10.1186/s12967-018-1588-2. View

Xin J, Song X . Role of peptidylarginine deiminase type 4 in gastric cancer. Exp Ther Med. 2016; 12(5):3155-3160. PMC: 5103760. DOI: 10.3892/etm.2016.3798. View

Kolodziej S, Kuvardina O, Oellerich T, Herglotz J, Backert I, Kohrs N . PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation. Nat Commun. 2014; 5:3995. PMC: 4050257. DOI: 10.1038/ncomms4995. View

Yu H, Tung C, Huang K, Huang H, Lu M . The Essential Role of Peptidylarginine Deiminases 2 for Cytokines Secretion, Apoptosis, and Cell Adhesion in Macrophage. Int J Mol Sci. 2020; 21(16). PMC: 7460808. DOI: 10.3390/ijms21165720. View

Chang X, Wu H, Li H, Li H, Zheng Y . PADI4 promotes epithelial-mesenchymal transition(EMT) in gastric cancer via the upregulation of interleukin 8. BMC Gastroenterol. 2022; 22(1):25. PMC: 8767667. DOI: 10.1186/s12876-022-02097-0. View

Okamato Y, Ghosh T, Okamoto T, Schuyler R, Seifert J, Charry L . Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4-and TLR-dependent enhanced histone H3 citrullination and proinflammatory cytokine production in CD14 monocytes. J Autoimmun. 2020; 117:102581. PMC: 7855988. DOI: 10.1016/j.jaut.2020.102581. View

Liu L, Zhang Z, Zhang G, Wang T, Ma Y, Guo W . Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib. J Transl Med. 2020; 18(1):357. PMC: 7504643. DOI: 10.1186/s12967-020-02528-0. View

Tian Y, Russo R, Li Y, Karmakar M, Liu B, Puskarich M . Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity. Infection. 2020; 49(1):83-93. PMC: 7527151. DOI: 10.1007/s15010-020-01528-y. View

Jang B, Shin H, Choi J, Nguyen D, Jeong B, Ishigami A . Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins. J Neuropathol Exp Neurol. 2011; 70(2):116-24. DOI: 10.1097/NEN.0b013e318207559e. View

10.

Khajavi M, Zhou Y, Birsner A, Bazinet L, Rosa Di Sant A, Schiffer A . Identification of Padi2 as a novel angiogenesis-regulating gene by genome association studies in mice. PLoS Genet. 2017; 13(6):e1006848. PMC: 5491319. DOI: 10.1371/journal.pgen.1006848. View

11.

Deng Q, Pan B, Alam H, Liang Y, Wu Z, Liu B . Citrullinated Histone H3 as a Therapeutic Target for Endotoxic Shock in Mice. Front Immunol. 2020; 10:2957. PMC: 6962130. DOI: 10.3389/fimmu.2019.02957. View

12.

Chang X, Hou X, Pan J, Fang K, Wang L, Han J . Investigating the pathogenic role of PADI4 in oesophageal cancer. Int J Biol Sci. 2011; 7(6):769-81. PMC: 3119849. DOI: 10.7150/ijbs.7.769. View

13.

Tanikawa C, Ueda K, Suzuki A, Iida A, Nakamura R, Atsuta N . Citrullination of RGG Motifs in FET Proteins by PAD4 Regulates Protein Aggregation and ALS Susceptibility. Cell Rep. 2018; 22(6):1473-1483. DOI: 10.1016/j.celrep.2018.01.031. View

14.

Xia X, Yan C, Wu W, Zhou Y, Hou L, Zuo B . Characterization of the porcine peptidylarginine deiminase type VI gene (PADI6) promoter: Sp1 regulates basal transcription of the porcine PADI6. Gene. 2015; 575(2 Pt 2):551-558. DOI: 10.1016/j.gene.2015.09.042. View

15.

Ying S, Kojima T, Kawada A, Nachat R, Serre G, Simon M . An intronic enhancer driven by NF-κB contributes to transcriptional regulation of peptidylarginine deiminase type I gene in human keratinocytes. J Invest Dermatol. 2010; 130(11):2543-52. DOI: 10.1038/jid.2010.179. View

16.

Shi L, Yao H, Liu Z, Xu M, Tsung A, Wang Y . Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis. Mol Cancer Res. 2020; 18(5):735-747. PMC: 7668292. DOI: 10.1158/1541-7786.MCR-19-0018. View

17.

Qu Y, Olsen J, Yuan X, Cheng P, Levesque M, Brokstad K . Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer. Nat Chem Biol. 2017; 14(1):94-101. DOI: 10.1038/nchembio.2510. View

18.

Wang Z, Shang J, Li C, Li M, Xing G . Significance of serum peptidylarginine deiminase type 4 in ANCA-associated vasculitis. Beijing Da Xue Xue Bao Yi Xue Ban. 2014; 46(2):200-6. View

19.

Gosswein S, Lindemann A, Mahajan A, Maueroder C, Martini E, Patankar J . Citrullination Licenses Calpain to Decondense Nuclei in Neutrophil Extracellular Trap Formation. Front Immunol. 2019; 10:2481. PMC: 6817590. DOI: 10.3389/fimmu.2019.02481. View

20.

Fei C, Zhou L . Gene mutations impede oocyte maturation, fertilization, and early embryonic development. Bioessays. 2022; 44(10):e2200007. DOI: 10.1002/bies.202200007. View