https://doi.org/10.4081/ejh.2024.4101
Deubiquitinase USP14 is upregulated in Crohn's disease and inhibits the NOD2 pathway mediated inflammatory response in vitro
Submitted: 8 July 2024
Accepted: 16 August 2024
Published: 9 September 2024
Accepted: 16 August 2024
Abstract Views: 377
PDF: 132
HTML: 1
HTML: 1
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The nucleotide binding oligomerization domain containing 2 (NOD2) protein and its ligand N-acetyl muramyl dipeptide (MDP) are crucially involved in Crohn’s disease (CD). However, the mechanism by which NOD2 signaling is regulated in CD patients remains unclear. Ubiquitin specific protease (USP14) is a deubiquitylase that plays an important role in immunity. This study aimed to investigate the mechanism by which UPS14 regulates NOD2 induced inflammatory response in CD and inflammatory bowel diseases (IBD). Our results showed that USP14 protein and mRNA levels in intestinal tissues of CD patients were significantly higher than those in healthy controls. In addition, USP14 was upregulated in IBD mouse model. While treatment with MDP, TNF-α or the Toll-like receptor 1/2 agonist Pam3CSK4 all led to significantly higher mRNA levels of TNF-α, IL-8 and IL-1β in THP-1 cells, pretreatment with USP14 inhibitor IU1 could stimulate further upregulation of TNF-α, IL-8 and IL-1β. In particular, MDP promoted the activation of JNK, ERK1/2 and p38 as well as NF-kB in THP-1 cells, and IU1 significantly enhanced the MDP-induced activation of these proteins without effects on USP14 protein level. Furthermore, the JNK inhibitor sp600125, ERK1/2 inhibitor U0126 or P38 MAPK inhibitor PD169316 significantly decreased the mRNA levels of TNF-α, IL-8 and IL-1β in THP-1 cells stimulated by both IU1 and MDP. In conclusion, our findings suggest that USP14 could inhibit MDP-induced activation of MAPK signaling and the inflammation response involved in IBD, and that USP14 is a potential therapeutic target for IBD.
Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010;28:573-621.
DOI: https://doi.org/10.1146/annurev-immunol-030409-101225
De Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 2017;14:739-49.
DOI: https://doi.org/10.1038/nrgastro.2017.110
Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015;12:205-17.
DOI: https://doi.org/10.1038/nrgastro.2015.34
Fritz T, Niederreiter L, Adolph T, Blumberg RS, Kaser A. Crohn's disease: NOD2, autophagy and ER stress converge. Gut 2011;60:1580-8.
DOI: https://doi.org/10.1136/gut.2009.206466
Ashton JJ, Seaby EG, Beattie RM, Ennis S. NOD2 in Crohn's disease-unfinished business. J Crohns Colitis. 2023;17:450-8.
DOI: https://doi.org/10.1093/ecco-jcc/jjac124
Sun Y, Qin Z, Li Q, Wan JJ, Cheng MH, Wang PY, et al. MicroRNA-124 negatively regulates LPS-induced TNF-α production in mouse macrophages by decreasing protein stability. Acta Pharmacol Sin. 2016;37:889-97.
DOI: https://doi.org/10.1038/aps.2016.16
Li H, Zhao Z, Ling J, Pan L, Zhao X, Zhu H, et al. USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses. Eur J Immunol 2019;49:42-53.
DOI: https://doi.org/10.1002/eji.201847603
Arbab A-a-I, Yin C, Lu X, Liang Y, Abdalla I-M, Idris A-A, et al. Metformin alleviates LTA-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells. Biocell 2022;46:2443-54.
DOI: https://doi.org/10.32604/biocell.2022.020865
Zhang H, Wang M, Xu Y. Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation. Cancer Biol Med 2023;20:268-86.
DOI: https://doi.org/10.20892/j.issn.2095-3941.2022.0547
Long Y, Zhao Y, Ma X, Zeng Y, Hu T, Wu W, et al. Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway. Eur J Histochem 2022;66:3415.
DOI: https://doi.org/10.4081/ejh.2022.3415
Liu Y, Chen H, Li G, Zhang J, Yao K, Wu C, et al. Radiotherapy delays malignant transformation and prolongs survival in patients with IDH-mutant gliomas. Cancer Biol Med 2022;19:1477-86.
DOI: https://doi.org/10.20892/j.issn.2095-3941.2022.0472
Kitaura H, Ishida M, Kimura K, Sugisawa H, Kishikawa A, Shima K, et al. Role of muramyl dipeptide in lipopolysaccharide-mediated biological activity and osteoclast Activity. Anal Cell Pathol (Amst) 2018;2018:8047610.
DOI: https://doi.org/10.1155/2018/8047610
da Paz Martins AS, Campos SBG, Goulart MOF, Moura FA. Extraintestinal manifestations of inflammatory bowel disease, nitroxidative stress and dysbiosis: What is the link between them? Biocell 2021; 45:461–81.
DOI: https://doi.org/10.32604/biocell.2021.014332
Lu J, Traub B, Kornmann M. The role of interleukin 13 receptor alpha 2 in inflammatory bowel disease and colorectal cancer. Transl Surg Oncol 2023;1:3-9.
Zhao Y, Zong F. Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF-κB signaling. Immun Inflamm Dis. 2021;9:1016-24.
DOI: https://doi.org/10.1002/iid3.465
Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014;14:329-42.
DOI: https://doi.org/10.1038/nri3661
Darling NJ, Cook SJ. The role of MAPK signaling pathways in the response to endoplasmic reticulum stress. Biochim Biophys Acta 2014;1843:2150-63.
DOI: https://doi.org/10.1016/j.bbamcr.2014.01.009
Hu T, Zhao Y, Long Y, Ma X, Zeng Y, Wu W, et al. TLR4 promoted endoplasmic reticulum stress induced inflammatory bowel disease via the activation of p38 MAPK pathway. Biosci Rep. 2022;42:BSR20220307.
DOI: https://doi.org/10.1042/BSR20220307
Woo SM, Kwon TK. E3 ubiquitin ligases and deubiquitinases as modulators of TRAIL-mediated extrinsic apoptotic signaling pathway. BMB Rep 2019;52:119-26.
DOI: https://doi.org/10.5483/BMBRep.2019.52.2.011
Zhu D, Zhang L, Shi X, Gao S, Yue C, Zhang L, et al. RNF43 is a novel tumor-suppressor and prognostic indicator in clear cell renal cell carcinoma. Oncol Res. 2022;29:159-74.
DOI: https://doi.org/10.32604/or.2022.03458
Zhang Y, Liu L, Luo B, Tang H, Yu X, Bao S. Calcyclin-binding protein contributes to cholangiocarcinoma progression by inhibiting ubiquitination of MCM2. Oncol Res 2023;31:317-31.
DOI: https://doi.org/10.32604/or.2023.028418
Zou M, Zeng QS, Nie J, Yang JH, Luo ZY, Gan HT. The role of E3 ubiquitin ligases and deubiquitinases in inflammatory bowel disease: friend or foe? Front Immunol 2021;12:769167.
DOI: https://doi.org/10.3389/fimmu.2021.769167
Pu S, Zheng H, Tao Y, Shao J, Yang M, Li S. The function of ubiquitin-specific protease 31 in intracerebral hemorrhage. Biocell 2022;46:1545-55.
DOI: https://doi.org/10.32604/biocell.2022.017544
Ethics Approval
this study was approved by Ethics Committee of Changsha Central Hospital (approval no. 2023036) and all patients provided informed consent, All animal experiments were reviewed and approved by the Institutional Animal Care Committee of University of South China (approval no. 2023094)Supporting Agencies
Natural Science Foundation of Hunan Province of ChinaHow to Cite
Li, M., Zhao, Y., Zhang, J., Jiang, W., Peng, S., Hu, J., & Shen, Y. (2024). Deubiquitinase USP14 is upregulated in Crohn’s disease and inhibits the NOD2 pathway mediated inflammatory response <i>in vitro</i>. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4101
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Federico Angelo Cazzaniga, Edoardo Bistaffa, Chiara Maria Giulia De Luca, Giuseppe Bufano, Antonio Indaco, Giorgio Giaccone, Fabio Moda, Sporadic Creutzfeldt-Jakob disease: Real-Time Quaking Induced Conversion (RT-QuIC) assay represents a major diagnostic advance , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
- G. Tsirakis, C. A. Pappa, M. Kaparou, V. Katsomitrou, A. Hatzivasili, T. Alegakis, A. Xekalou, E. N. Stathopoulos, M. Alexandrakis, Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients , European Journal of Histochemistry: Vol. 55 No. 3 (2011)
- Yan Long, Yan Zhao, Xiaoqing Ma, Ya Zeng, Tian Hu, Weijie Wu, Chongtian Deng, Jinyue Hu, Yueming Shen, Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- C. Severi, R. Sferra, A. Scirocco, A. Vetuschi, N. Pallotta, A. Pronio, R. Caronna, G. Di Rocco, E. Gaudio, E. Corazziari, P. Onori, Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis , European Journal of Histochemistry: Vol. 58 No. 4 (2014)
- Y. Kaneko, N. Onda, Y. Watanabe, M. Shibutani, Identification of 5-hydroxytryptamine-producing cells by detection of fluorescence in paraffin-embedded tissue sections , European Journal of Histochemistry: Vol. 60 No. 3 (2016)
- M. Di Rosa, M.A. Szychlinska, D. Tibullo, L. Malaguarnera, G. Musumeci, Expression of CHI3L1 and CHIT1 in osteoarthritic rat cartilage model. A morphological study , European Journal of Histochemistry: Vol. 58 No. 3 (2014)
- R. Leonardi, R.E. Perrotta, C. Loreto, G. Musumeci, S. Crimi, J.N. dos Santos, M.C. Rusu, P. Bufo, E. Barbato, G. Pannone, Toll-like receptor 4 expression in the epithelium of inflammatory periapical lesions. An immunohistochemical study , European Journal of Histochemistry: Vol. 59 No. 4 (2015)
- Francesca Diomede, Soundara Rajan Thangavelu, Ilaria Merciaro, Monica D'Orazio, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani, Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells: role of epigenetic modifications to the inflammation , European Journal of Histochemistry: Vol. 61 No. 3 (2017)
- Yongwei Lin, Zhipeng Zhou, Lang Xie, Yongsheng Huang, Zhenghua Qiu, Lili Ye, Chunhui Cui, Effects of miR-939 and miR-376A on ulcerative colitis using a decoy strategy to inhibit NF-κB and NFAT expression , European Journal of Histochemistry: Vol. 66 No. 1 (2022)
- Carolina Pellegrini, Vanessa D'Antongiovanni, Chiara Ippolito, Cristina Segnani, Luca Antonioli, Matteo Fornai, Nunzia Bernardini, From the intestinal mucosal barrier to the enteric neuromuscular compartment: an integrated overview on the morphological changes in Parkinson’s disease , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
You may also start an advanced similarity search for this article.
