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内质网应激在溃疡性结肠炎中作用机制的研究进展
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Abstract:
内质网应激是细胞的重要防御机制，最大限度地对抗内外源性的应激，应激可激活下游信号使得蛋白折叠功能恢复或细胞死亡，持续高强度的内质网应激则会触发程序性细胞死亡或者是凋亡。在溃疡性结肠炎的发生发展中内质网应激发挥了重要作用。现对内质网应激在溃疡性结肠炎中的研究进展进行综述，为溃疡性结肠炎的治疗提供新思路。
Endoplasmic reticulum stress is an important defense mechanism of cells, which can maximize the resistance to internal and external stress. Stress can activate downstream signals to restore protein folding function or cell death, and sustained high intensity endoplasmic reticulum stress can trigger programmed cell death or apoptosis. Endoplasmic reticulum stress plays an important role in the occurrence and development of ulcerative colitis. This article reviews the research progress of endoplasmic reticulum stress in ulcerative colitis, and provides a new idea for the treatment of ulcerative colitis.
| [1] | Park, S.H. and Park, S.H. (2022) Personalized Medicine in Inflammatory Bowel Disease: Perspectives on Asia. Journal of Gastroenterology and Hepatology, 37, 1434-1445. https://doi.org/10.1111/jgh.15919 |
| [2] | Ng, S.C., Shi, H.Y., Hamidi, N., et al. (2017) Worldwide Incidence and Prevalence of Inflammatory Bowel Disease in the 21st Century: A Systematic Review of Population-Based Studies. The Lancet, 390, 2769-2778. https://doi.org/10.1016/S0140-6736(17)32448-0 |
| [3] | Kaplan, G.G. (2015) The Global Burden of IBD: From 2015 to 2025. Nature Reviews Gastroenterology & Hepatology, 12, 720-727. https://doi.org/10.1038/nrgastro.2015.150 |
| [4] | 尹硕鑫, 张涛, 王舒萍, 等. 维得利珠单抗诱导和维持炎症性肠病疗效Meta分析[J]. 陕西医学杂志, 2022, 51(1): 103-110. |
| [5] | Maloy, K.J. and Powrie, F. (2011) Intestinal Homeostasis and Its Breakdown in Inflammatory Bowel Disease. Nature, 474, 298-306. https://doi.org/10.1038/nature10208 |
| [6] | Qiao, D., Zhang, Z., Zhang, Y., Chen, Q., Chen, Y., Tang, Y., et al. (2021) Regulation of Endoplasmic Reticulum Stress-Autophagy: A Potential Therapeutic Target for Ulcerative Colitis. Frontiers in Pharmacology, 12, Article 697360. https://doi.org/10.3389/fphar.2021.697360 |
| [7] | Roda, G. (2010) Intestinal Epithelial Cells in Inflammatory Bowel Diseases. World Journal of Gastroenterology, 16, 4264-4271. https://doi.org/10.3748/wjg.v16.i34.4264 |
| [8] | Bevins, C.L. and Salzman, N.H. (2011) Paneth Cells, Antimicrobial Peptides and Maintenance of Intestinal Homeostasis. Nature Reviews Microbiology, 9, 356-368. https://doi.org/10.1038/nrmicro2546 |
| [9] | Goto, Y. and Kiyono, H. (2015) Epithelial Barrier: An Interface for the Cross-Communication between Gut Flora and Immune System. Immunological Reviews, 245, 147-163. https://doi.org/10.1111/j.1600-065X.2011.01078.x |
| [10] | Gill, N., Wlodarska, M. and Finlay, B.B. (2011) Roadblocks in the Gut: Barriers to Enteric Infection. Cellular Microbiology, 13, 660-669. https://doi.org/10.1111/j.1462-5822.2011.01578.x |
| [11] | Bischoff, S.C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J., Serino, M., et al. (2014) Intestinal Permeability—A New Target for Disease Prevention and Therapy. BMC Gastroenterology, 14, Article No. 189. https://doi.org/10.1186/s12876-014-0189-7 |
| [12] | Michielan, A. and D’Incà, R. (2015) Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. Mediators of Inflammation, 2015, Article ID: 628157. https://doi.org/10.1155/2015/628157 |
| [13] | Szabo, G. (2015) Gut-Liver Axis in Alcoholic Liver Disease. Gastroenterology, 148, 30-36. https://doi.org/10.1053/j.gastro.2014.10.042 |
| [14] | Rutkowski, D.T. and Hegde, R.S. (2010) Regulation of Basal Cellular Physiology by the Homeostatic Unfolded Protein Response. Journal of Cell Biology, 189, 783-794. https://doi.org/10.1083/jcb.201003138 |
| [15] | Grootjans, J., Kaser, A., Kaufman, R.J. and Blumberg, R.S. (2016) The Unfolded Protein Response in Immunity and Inflammation. Nature Reviews Immunology, 16, 469-484. https://doi.org/10.1038/nri.2016.62 |
| [16] | 郑烈, 张亚利, 戴彦成, 等. 健脾清肠方含药血清对HT29细胞内质网应激模型NF-κB信号通路的影响[J]. 中华中医药杂志, 2019, 34(3): 1194-1197. |
| [17] | Jiang, Y., Zhang, C. and Wang, T. (2020) bFGF Ameliorates Intestinal Mucosal Permeability and Barrier Function through Tight Junction Proteins in Burn Injury Rats. Burns, 47, 1129-1136. https://doi.org/10.1016/j.burns.2020.11.004 |
| [18] | Slifer, Z.M. and Blikslager, A.T. (2020) The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium. International Journal of Molecular Sciences, 21, Article 972. https://doi.org/10.3390/ijms21030972 |
| [19] | 靳宇航, 贾海, 王仁杰, 等. 内质网应激信号影响猪肠道屏障功能的研究进展[J]. 动物营养学报, 2021, 33(6): 3072-3080. |
| [20] | Long, M., Chen, X., Wang, N., Wang, M., Pan, J., Tong, J., et al. (2018) Proanthocyanidins Protect Epithelial Cells from Zearalenone-Induced Apoptosis via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis Pathways in Mouse Small Intestines. Molecules, 23, Article 1508. https://doi.org/10.3390/molecules23071508 |
| [21] | Li, N., Wang, X., Jiang, L., Zhang, M., Li, N., Wei, Z., et al. (2016) Effects of Endoplasmic Reticulum Stress on the Expression of Inflammatory Cytokines in Patients with Ulcerative Colitis. World Journal of Gastroenterology, 22, 2357-2365. https://doi.org/10.3748/wjg.v22.i7.2357 |
| [22] | Cao, S.S. (2016) Epithelial ER Stress in Crohnʼs Disease and Ulcerative Colitis. Inflammatory Bowel Diseases, 22, 984-993. https://doi.org/10.1097/mib.0000000000000660 |
| [23] | Schwarz, D.S. and Blower, M.D. (2015) The Endoplasmic Reticulum: Structure, Function and Response to Cellular Signaling. Cellular and Molecular Life Sciences, 73, 79-94. https://doi.org/10.1007/s00018-015-2052-6 |
| [24] | Walter, P. and Ron, D. (2011) The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation. Science, 334, 1081-1086. https://doi.org/10.1126/science.1209038 |
| [25] | Chen, X. and Cubillos-Ruiz, J.R. (2020) Endoplasmic Reticulum Stress Signals in the Tumour and Its Microenvironment. Nature Reviews Cancer, 21, 71-88. https://doi.org/10.1038/s41568-020-00312-2 |
| [26] | Cao, S.S. and Kaufman, R.J. (2012) Unfolded Protein Response. Current Biology, 22, R622-R626. https://doi.org/10.1016/j.cub.2012.07.004 |
| [27] | Almanza, A., et al. (2018) Endoplasmic Reticulum Stress Signalling—From Basic Mechanisms to Clinical Applications. FEBS Journal, 286, 241-278. https://doi.org/10.1111/febs.14608 |
| [28] | Kaser, A., Lee, A., Franke, A., Glickman, J.N., Zeissig, S., Tilg, H., et al. (2008) XBP1 Links ER Stress to Intestinal Inflammation and Confers Genetic Risk for Human Inflammatory Bowel Disease. Cell, 134, 743-756. https://doi.org/10.1016/j.cell.2008.07.021 |
| [29] | Hetz, C. (2024) The Unfolded Protein Response: Controlling Cell Fate Decisions under ER Stress and beyond. Nature Reviews Molecular Cell Biology, 13, 89-102. https://doi.org/10.1038/nrm3270 |
| [30] | Bogaert, S., De Vos, M., Olievier, K., Peeters, H., Elewaut, D., Lambrecht, B., et al. (2011) Involvement of Endoplasmic Reticulum Stress in Inflammatory Bowel Disease: A Different Implication for Colonic and Ileal Disease? PLOS ONE, 6, e25589. https://doi.org/10.1371/journal.pone.0025589 |
| [31] | Zhang, Z., Qian, Q., Li, M., et al. (2020) The Unfolded Protein Response Regulates Hepatic Autophagy by sXBP1-mediated Activation of TFEB. Autophagy, 17, 1841-1855. https://doi.org/10.1080/15548627.2020.1788889 |
| [32] | Le, Q.G. and Kimata, Y. (2021) Multiple Ways for Stress Sensing and Regulation of the Endoplasmic Reticulum-Stress Sensors. Cell Structure and Function, 46, 37-49. https://doi.org/10.1247/csf.21015 |
| [33] | Urra, H., Dufey, E., Lisbona, F., Rojas-Rivera, D. and Hetz, C. (2013) When ER Stress Reaches a Dead End. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1833, 3507-3517. https://doi.org/10.1016/j.bbamcr.2013.07.024 |
| [34] | Wu, H., Guo, H., Liu, H., Cui, H., Fang, J., Zuo, Z., et al. (2020) Copper Sulfate-Induced Endoplasmic Reticulum Stress Promotes Hepatic Apoptosis by Activating CHOP, JNK and Caspase-12 Signaling Pathways. Ecotoxicology and Environmental Safety, 191, Article ID: 110236. https://doi.org/10.1016/j.ecoenv.2020.110236 |
| [35] | 陈鹏, 聂源, 朱萱. 内质网应激信号通路在肝纤维化中的研究进展[J]. 生命科学, 2022, 34(11): 1402-1408. |
| [36] | Karagöz, G.E., Acosta-Alvear, D., Nguyen, H.T., Lee, C.P., Chu, F. and Walter, P. (2017) An Unfolded Protein-Induced Conformational Switch Activates Mammalian IRE1. eLife, 6, e30700. https://doi.org/10.7554/elife.30700 |
| [37] | Men, L., Yu, S., Yao, J., Li, Y., Ren, D. and Du, J. (2018) Selenoprotein S Protects against Adipocyte Death through Mediation of the IRE1α-sXBP11 Pathway. Biochemical and Biophysical Research Communications, 503, 2866-2871. https://doi.org/10.1016/j.bbrc.2018.08.057 |
| [38] | Shan, B., Wang, X., Wu, Y., Xu, C., Xia, Z., Dai, J., et al. (2017) The Metabolic ER Stress Sensor Ire1α Suppresses Alternative Activation of Macrophages and Impairs Energy Expenditure in Obesity. Nature Immunology, 18, 519-529. https://doi.org/10.1038/ni.3709 |
| [39] | Hollien, J., Lin, J.H., Li, H., Stevens, N., Walter, P. and Weissman, J.S. (2009) Regulated IRE1-Dependent Decay of Messenger RNAs in Mammalian Cells. Journal of Cell Biology, 186, 323-331. https://doi.org/10.1083/jcb.200903014 |
| [40] | Camarillo, G.F., Goyon, E.I., Zuñiga, R.B., Salas, L.A.S., Escárcega, A.E.P. and Yamamoto-Furusho, J.K. (2020) Gene Expression Profiling of Mediators Associated with the Inflammatory Pathways in the Intestinal Tissue from Patients with Ulcerative Colitis. Mediators of Inflammation, 2020, Article ID: 9238970. https://doi.org/10.1155/2020/9238970 |
| [41] | Kaser, A., Adolph, T.E. and Blumberg, R.S. (2013) The Unfolded Protein Response and Gastrointestinal Disease. Seminars in Immunopathology, 35, 307-319. https://doi.org/10.1007/s00281-013-0377-5 |
| [42] | Chen, Y., Wu, Z.Y., Huang, S.J., et al. (2022) Adipocyte IRE1α promotes PGC1α mRNA Decay and Restrains Adaptive Thermo-Genesis. Nature Metabolism, 4, 1166-1184. |
| [43] | 罗琦琦, 曲光瑾, 罗善顺. 微RNAs与内质网应激信号通路的相互调控作用[J]. 中国生物化学与分子生物学报, 2022, 38(2): 191-196. |
| [44] | Zhang, B., Su, X.Y., Xie, Z.Y., et al. (2020) Inositol-Requiring Kinase 1 Regulates Apoptosis via Inducing Endoplasmic Reticulum Stress in Colitis Epithelial Cells. Digestive Diseases and Sciences, 66, 3015-3025. https://doi.org/10.1007/s10620-020-06622-7 |
| [45] | 张雅丽, 孙佳宁, 战晶玉, 等. 连草泻痢胶囊对溃疡性结肠炎大鼠内质网应激及炎症反应的影响[J]. 中国中医药信息杂志, 2023, 30(5): 97-103. |
| [46] | Xu, F., Du, W., Zou, Q., Wang, Y., Zhang, X., Xing, X., et al. (2020) COPII Mitigates ER Stress by Promoting Formation of ER Whorls. Cell Research, 31, 141-156. https://doi.org/10.1038/s41422-020-00416-2 |
| [47] | Rozpędek, W., Pytel, D., Diehl, J.A., et al. (2016) Small Molecule Inhibitors of PERK-Dependent Signaling Pathway as a Novel, Therapeutic Molecular Strategy in Alzheimer’s Disease Treatment. Polski Merkuriusz Lekarski, 41, 5-10. |
| [48] | George, A.K., Behera, J., Kelly, K.E., Mondal, N.K., Richardson, K.P. and Tyagi, N. (2018) Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling. Scientific Reports, 8, Article No. 5158. https://doi.org/10.1038/s41598-018-23568-z |
| [49] | Marciniak, S.J., Yun, C.Y., Oyadomari, S., Novoa, I., Zhang, Y., Jungreis, R., et al. (2004) CHOP Induces Death by Promoting Protein Synthesis and Oxidation in the Stressed Endoplasmic Reticulum. Genes & Development, 18, 3066-3077. https://doi.org/10.1101/gad.1250704 |
| [50] | Hu, H., Tian, M., Ding, C. and Yu, S. (2019) The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection. Frontiers in Immunology, 9, Article 3083. https://doi.org/10.3389/fimmu.2018.03083 |
| [51] | Zhang, S.X., Sanders, E., Fliesler, S.J. and Wang, J.J. (2014) Endoplasmic Reticulum Stress and the Unfolded Protein Responses in Retinal Degeneration. Experimental Eye Research, 125, 30-40. https://doi.org/10.1016/j.exer.2014.04.015 |
| [52] | Palam, L.R., Baird, T.D. and Wek, R.C. (2011) Phosphorylation of eIF2 Facilitates Ribosomal Bypass of an Inhibitory Upstream ORF to Enhance CHOP Translation. Journal of Biological Chemistry, 286, 10939-10949. https://doi.org/10.1074/jbc.m110.216093 |
| [53] | Feng, K., Ge, Y., Chen, Z., Li, X., Liu, Z., Li, X., et al. (2019) Curcumin Inhibits the Perk-eIF2α-Chop Pathway through Promoting SIRT1 Expression in Oxidative Stress-Induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model. Oxidative Medicine and Cellular Longevity, 2019, Article ID: 8574386. https://doi.org/10.1155/2019/8574386 |
| [54] | Hu, X., Duan, T., Wu, Z., Tang, C. and Cao, Z. (2021) Puerarin Inhibits the PERK-eIF2α-ATF4-CHOP Pathway through Inactivating JAK2/STAT3 Signal in Pancreatic β-Cells. The American Journal of Chinese Medicine, 49, 1723-1738. https://doi.org/10.1142/s0192415x21500816 |
| [55] | Lu, P.D., Harding, H.P. and Ron, D. (2004) Translation Reinitiation at Alternative Open Reading Frames Regulates Gene Expression in an Integrated Stress Response. The Journal of Cell Biology, 167, 27-33. https://doi.org/10.1083/jcb.200408003 |
| [56] | Hu Hai, Tian Ming-Xing, Ding Chan. CHOP调控内质网应激介导细胞凋亡的机制[J]. 中国预防兽医学报, 2019, 41(2): 219. |
| [57] | Hooper, K.M., Barlow, P.G., Henderson, P. and Stevens, C. (2018) Interactions between Autophagy and the Unfolded Protein Response: Implications for Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 25, 661-671. https://doi.org/10.1093/ibd/izy380 |
| [58] | Rodrigues, B.L., Dotti, I., Pascoal, L.B., Morari, J., Esteller, M., Coope, A., et al. (2022) Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation. Mediators of Inflammation, 2022, Article ID: 6049500. https://doi.org/10.1155/2022/6049500 |
| [59] | 罗敏, 杜英杰, 姜燕诗, 等. 基于内质网应激PERK信号通路探讨芍药汤对UC大鼠的作用机制[J]. 湖南中医药大学学报, 2021, 41(11): 1663-1668. |
| [60] | 朱玉梅, 董筠. 中医药治疗溃疡性结肠炎研究进展[J]. 河南中医, 2021, 41(7): 1121-1125. |
| [61] | 王金钢, 陈春晓, 任于晗, 等. 二甲双胍通过抑制内质网应激诱导的细胞凋亡改善结肠炎黏膜上皮屏障损伤[J]. 浙江大学学报(医学版), 2021, 50(5): 627-632. |
| [62] | 吴志强, 肖玉娇, 谷丽瑶, 等. 基于PERK信号通路介导的细胞凋亡及杯状细胞破坏探讨芍药汤对溃疡性结肠炎大鼠的作用机制[J]. 陕西中医, 2022, 43(11): 1511-1515. |
| [63] | 郑春菊, 王斌, 赵恩春, 等. 基于疏肝健脾法的怡情止泻汤调控内质网应激/NF-κB通路治疗溃疡性结肠炎[J]. 中药药理与临床, 2022, 38(2): 173-178. |
| [64] | 莫达瑜, 刘英超, 江向红, 等. 甘草酸苷调节内质网应激PERK-elF2α-NF-κB信号通路治疗溃疡性结肠炎的机制研究[J]. 时珍国医国药, 2022, 33(8): 1860-1864. |
| [65] | 沈雁, 王章流, 钟继红, 等. 基于PERK-eIF2α-NF-κB信号通路研究甘草酸苷对小鼠肠上皮细胞内质网应激的保护作用[J]. 中国现代应用药学, 2022, 39(11): 1389-1394. |
| [66] | Wu, Y.Y., Liu, M.J., Yin, S.J., et al. (2020) Acupuncture Reduce Colonic Inflammation by Suppressing Oxidative Stress and Endo-Plasmic Reticulum Stress in Rats with Ulcerative Colitis. Acupuncture Research, 45, 8-13. |
| [67] | Adachi, Y., Yamamoto, K., Okada, T., Yoshida, H., Harada, A. and Mori, K. (2008) ATF6 Is a Transcription Factor Specializing in the Regulation of Quality Control Proteins in the Endoplasmic Reticulum. Cell Structure and Function, 33, 75-89. https://doi.org/10.1247/csf.07044 |
| [68] | Wu, J., et al. (2007) ATF6α Optimizes Long-Term Endoplasmic Reticulum Function to Protect Cells from Chronic Stress. Developmental Cell, 13, 351-364. https://doi.org/10.1016/j.devcel.2007.07.005 |
| [69] | Sharma, R.B., Darko, C. and Alonso, L.C. (2020) Intersection of the ATF6 and XBP1 ER Stress Pathways in Mouse Islet Cells. Journal of Biological Chemistry, 295, 14164-14177. https://doi.org/10.1074/jbc.ra120.014173 |
| [70] | Walter, F., O’Brien, A., Concannon, C.G., Düssmann, H. and Prehn, J.H.M. (2018) ER Stress Signaling Has an Activating Transcription Factor 6α (atf6)-Dependent “Off-Switch”. Journal of Biological Chemistry, 293, 18270-18284. https://doi.org/10.1074/jbc.ra118.002121 |
| [71] | Han, L., Xu, Y.H. and Shi, Y.X. (2021) Molecular Mechanism of ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuron Apoptosis in SPS Rats. Journal of Molecular Neuroscience. https://doi.org/10.21203/rs.3.rs-170376/v1 |
| [72] | So, J. (2019) Erratum to: Roles of Endoplasmic Reticulum Stress in Immune Responses. Molecules and Cells, 42, 501-501. https://doi.org/10.14348/molcells.2019.1241 |
| [73] | Cao, S.S., et al. (2013) The Unfolded Protein Response and Chemical Chaperones Reduce Protein Misfolding and Colitis in Mice. Gastroenterology, 144, 989-1000. https://doi.org/10.1053/j.gastro.2013.01.023 |
| [74] | Cao, S.S., Zimmermann, E.M., Chuang, B., Song, B., Nwokoye, A., Wilkinson, J.E., et al. (2013) The Unfolded Protein Response and Chemical Chaperones Reduce Protein Misfolding and Colitis in Mice. Gastroenterology, 144, 989-1000.e6. https://doi.org/10.1053/j.gastro.2013.01.023 |
| [75] | Negroni, A., et al. (2014) Endoplasmic Reticulum Stress and Unfolded Protein Response Are Involved in Paediatric Inflammatory Bowel Disease. Digestive & Liver Disease, 46, 788-794. https://doi.org/10.1016/j.dld.2014.05.013 |
