Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

miR-29c-3p Accelerates Mucosal Repair in Dextran Sodium Sulfateinduced Ulcerative Colitis Mice through the KDM6B/H3K27me3/LDHA Axis

Author(s): Xia Li*, Chuanming Yin and Jie Li

Volume 30, Issue 6, 2023

Published on: 05 June, 2023

Page: [459 - 468] Pages: 10

DOI: 10.2174/0929866530666230511115213

Price: $65

Abstract

Background: Ulcerative colitis (UC) is an inflammatory intestinal disorder featured by mucosal injury. MicroRNAs (miRNAs) play a role in the pathogenesis underlying UC.

Objectives: This study was conducted to investigate the role of miR-29c-3p in a dextran sodium sulfate (DSS)-induced UC mouse model and provide targets for UC treatment.

Methods: The UC mouse model was established by DSS induction. The expression levels of miR- 29c-3p, lysine-specific demethylase 6B (KDM6B), zonula occludens-1 (ZO-1), Occludin, and lactate dehydrogenase A (LDHA) were detected by real-time quantitative polymerase chain reaction or Western blot assays. The mucosal injury was evaluated by disease activity index (DAI), colon length, Hematoxylin-Eosin staining, and fluorescein isothiocyanate-glucan permeability test. The binding between miR-29c-3p and KDM6B and the occupation of KDM6B or trimethylated H3 lysine 27 (H3K27me3) on the LDHA promoter were analyzed by the dual-luciferase and chromatinimmunoprecipitation assays.

Results: miR-29c-3p was downregulated while KDM6B and LDHA were upregulated in DSS mice. miR-29c-3p overexpression reduced DAI and inflammatory cell infiltration while increasing colon length, intestinal permeability, and levels of ZO-1 and Occludin. miR-29c-3p inhibited KDM6B expression and increased H3K27me3 occupation on the LDHA promoter, thus inhibiting LDHA transcription. Overexpression of KDM6B or LDHA averted the protective role of miR-29c-3p upregulation in mucosal injury.

Conclusion: miR-29c-3p limited KDM6B expression and increased the H3K27me3 occupation on the LDHA promoter to enhance LDHA transcription, moderating mucosal injury and delaying UC progression.

« Previous Next »
Graphical Abstract

[1]
Segal, J.P.; LeBlanc, J.F.; Hart, A.L. Ulcerative colitis: An update. Clin. Med., 2021, 21(2), 135-139.
[http://dx.doi.org/10.7861/clinmed.2021-0080] [PMID: 33762374]
[2]
Feuerstein, J.D.; Moss, A.C.; Farraye, F.A. Ulcerative Colitis. Mayo Clin. Proc., 2019, 94(7), 1357-1373.
[http://dx.doi.org/10.1016/j.mayocp.2019.01.018] [PMID: 31272578]
[3]
Tatiya-aphiradee, N.; Chatuphonprasert, W.; Jarukamjorn, K. Immune response and inflammatory pathway of ulcerative colitis. J. Basic Clin. Physiol. Pharmacol., 2018, 30(1), 1-10.
[http://dx.doi.org/10.1515/jbcpp-2018-0036] [PMID: 30063466]
[4]
Eisenstein, M. Ulcerative colitis: Towards remission. Nature, 2018, 563(7730), S33.
[http://dx.doi.org/10.1038/d41586-018-07276-2] [PMID: 30405234]
[5]
Nascimento, R.P.; Machado, A.P.F.; Galvez, J.; Cazarin, C.B.B.; Maróstica, Junior M.R. Ulcerative colitis: Gut microbiota, immunopathogenesis and application of natural products in animal models. Life Sci., 2020, 258, 118129.
[http://dx.doi.org/10.1016/j.lfs.2020.118129] [PMID: 32717271]
[6]
Chen, L.; Heikkinen, L.; Wang, C.; Yang, Y.; Sun, H.; Wong, G. Trends in the development of miRNA bioinformatics tools. Brief. Bioinform., 2019, 20(5), 1836-1852.
[http://dx.doi.org/10.1093/bib/bby054] [PMID: 29982332]
[7]
Singh, R.P.; Massachi, I.; Manickavel, S.; Singh, S.; Rao, N.P.; Hasan, S.; Mc Curdy, D.K.; Sharma, S.; Wong, D.; Hahn, B.H.; Rehimi, H. The role of miRNA in inflammation and autoimmunity. Autoimmun. Rev., 2013, 12(12), 1160-1165.
[http://dx.doi.org/10.1016/j.autrev.2013.07.003] [PMID: 23860189]
[8]
Zhou, J.; Liu, J.; Gao, Y.; Shen, L.; Li, S.; Chen, S. miRNA-based potential biomarkers and new molecular insights in ulcerative colitis. Front. Pharmacol., 2021, 12, 707776.
[http://dx.doi.org/10.3389/fphar.2021.707776] [PMID: 34305614]
[9]
Horita, M.; Farquharson, C.; Stephen, L.A. The role of miR‐29 family in disease. J. Cell. Biochem., 2021, 122(7), 696-715.
[http://dx.doi.org/10.1002/jcb.29896] [PMID: 33529442]
[10]
Cron, M.A.; Payet, C.A.; Fayet, O.M.; Maillard, S.; Truffault, F.; Fadel, E.; Guihaire, J.; Berrih-Aknin, S.; Liston, A.; Le Panse, R. Decreased expression of miR-29 family associated with autoimmune myasthenia gravis. J. Neuroinflammation, 2020, 17(1), 294.
[http://dx.doi.org/10.1186/s12974-020-01958-3] [PMID: 33032631]
[11]
Sun, Y.; Zhou, Y.; Shi, Y.; Zhang, Y.; Liu, K.; Liang, R.; Sun, P.; Chang, X.; Tang, W.; Zhang, Y.; Li, J.; Wang, S.; Zhu, Y.; Han, X. Expression of miRNA-29 in pancreatic β cells promotes inflammation and diabetes via TRAF3. Cell Rep., 2021, 34(1), 108576.
[http://dx.doi.org/10.1016/j.celrep.2020.108576] [PMID: 33406428]
[12]
Guo, J.; Zhang, R.; Zhao, Y.; Wang, J. MiRNA-29c-3p promotes intestinal inflammation via targeting leukemia inhibitory factor in ulcerative colitis. J. Inflamm. Res., 2021, 14, 2031-2043.
[http://dx.doi.org/10.2147/JIR.S302832] [PMID: 34040415]
[13]
Hyun, K.; Jeon, J.; Park, K.; Kim, J. Writing, erasing and reading histone lysine methylations. Exp. Mol. Med., 2017, 49(4), e324.
[http://dx.doi.org/10.1038/emm.2017.11] [PMID: 28450737]
[14]
Ma, S.; Xu, L.; Chen, L.; Sun, X.; Hu, F.; Gong, Y.; Yang, R.; Li, J.; Wang, Q.; Huang, S.; Zhou, H.; Wang, J. Novel pharmacological inhibition of JMJD3 improves necrotizing enterocolitis by attenuating the inflammatory response and ameliorating intestinal injury. Biochem. Pharmacol., 2022, 203, 115165.
[http://dx.doi.org/10.1016/j.bcp.2022.115165] [PMID: 35803318]
[15]
Xiao, X.; Huang, X.; Ye, F.; Chen, B.; Song, C.; Wen, J.; Zhang, Z.; Zheng, G.; Tang, H.; Xie, X. The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer. Sci. Rep., 2016, 6(1), 21735.
[http://dx.doi.org/10.1038/srep21735] [PMID: 26902416]
[16]
Jiang, Y.; Li, F.; Gao, B.; Ma, M.; Chen, M.; Wu, Y.; Zhang, W.; Sun, Y.; Liu, S.; Shen, H. KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma. Theranostics, 2021, 11(8), 3868-3881.
[http://dx.doi.org/10.7150/thno.53347] [PMID: 33664867]
[17]
Ni, S.; Liu, Y.; Zhong, J.; Shen, Y. Inhibition of LncRNA-NEAT1 alleviates intestinal epithelial cells (IECs) dysfunction in ulcerative colitis by maintaining the homeostasis of the glucose metabolism through the miR-410-3p-LDHA axis. Bioengineered, 2022, 13(4), 8961-8971.
[http://dx.doi.org/10.1080/21655979.2022.2037957] [PMID: 35735114]
[18]
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals.Guide for the Care and Use of Laboratory Animals; 8th ed.; National Academies Press (US): Washington (DC), 2011.
[19]
Zaki, M.H.; Boyd, K.L.; Vogel, P.; Kastan, M.B.; Lamkanfi, M.; Kanneganti, T.D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity, 2010, 32(3), 379-391.
[http://dx.doi.org/10.1016/j.immuni.2010.03.003] [PMID: 20303296]
[20]
Liu, S.; Zhang, S.; Lv, X.; Lu, J.; Ren, C.; Zeng, Z.; Zheng, L.; Zhou, X.; Fu, H.; Zhou, D.; Chen, Y. Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway. Int. Immunopharmacol., 2019, 75, 105768.
[http://dx.doi.org/10.1016/j.intimp.2019.105768] [PMID: 31382166]
[21]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[22]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(D1), D92-D97.
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[23]
Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015, 4, e05005.
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[24]
Miranda, K.C.; Huynh, T.; Tay, Y.; Ang, Y.S.; Tam, W.L.; Thomson, A.M.; Lim, B.; Rigoutsos, I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell, 2006, 126(6), 1203-1217.
[http://dx.doi.org/10.1016/j.cell.2006.07.031] [PMID: 16990141]
[25]
Leng, X.Y.; Yang, J.; Fan, H.; Chen, Q.Y.; Cheng, B.J.; He, H.X.; Gao, F.; Zhu, F.; Yu, T.; Liu, Y.J. JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis. Int. Immunopharmacol., 2022, 110, 109000.
[http://dx.doi.org/10.1016/j.intimp.2022.109000] [PMID: 35777266]
[26]
Boal Carvalho, P.; Cotter, J. mucosal healing in ulcerative colitis: A comprehensive review. Drugs, 2017, 77(2), 159-173.
[http://dx.doi.org/10.1007/s40265-016-0676-y] [PMID: 28078646]
[27]
Tang, S.; Guo, W.; Kang, L.; Liang, J. MiRNA-182-5p aggravates experimental ulcerative colitis via sponging Claudin-2. J. Mol. Histol., 2021, 52(6), 1215-1224.
[http://dx.doi.org/10.1007/s10735-021-10021-1] [PMID: 34623552]
[28]
Nijhuis, A.; Biancheri, P.; Lewis, A.; Bishop, C.L.; Giuffrida, P.; Chan, C.; Feakins, R.; Poulsom, R.; Di Sabatino, A.; Corazza, G.R.; MacDonald, T.T.; Lindsay, J.O.; Silver, A.R. In Crohn’s disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. Clin. Sci., 2014, 127(5), 341-350.
[http://dx.doi.org/10.1042/CS20140048] [PMID: 24641356]
[29]
Xiao, L.; Ma, X.X.; Luo, J.; Chung, H.K.; Kwon, M.S.; Yu, T.X.; Rao, J.N.; Kozar, R.; Gorospe, M.; Wang, J.Y. Circular RNA CircHIPK3 promotes homeostasis of the intestinal epithelium by reducing MicroRNA 29b function. Gastroenterology, 2021, 161(4), 1303-1317.e3.
[http://dx.doi.org/10.1053/j.gastro.2021.05.060] [PMID: 34116030]
[30]
Zhu, Y.; Wang, W.; Yuan, T.; Fu, L.; Zhou, L.; Lin, G.; Zhao, S.; Zhou, H.; Wu, G.; Wang, J. MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig. Am. J. Physiol. Gastrointest. Liver Physiol., 2017, 312(5), G434-G442.
[http://dx.doi.org/10.1152/ajpgi.00020.2017] [PMID: 28280141]
[31]
Ibrahim, S.; Zhu, X.; Luo, X.; Feng, Y.; Wang, J. PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease. Int. Immunopharmacol., 2020, 85, 106610.
[http://dx.doi.org/10.1016/j.intimp.2020.106610] [PMID: 32473571]
[32]
Kuo, W.T.; Zuo, L.; Odenwald, M.A.; Madha, S.; Singh, G.; Gurniak, C.B.; Abraham, C.; Turner, J.R. The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair. Gastroenterology, 2021, 161(6), 1924-1939.
[http://dx.doi.org/10.1053/j.gastro.2021.08.047] [PMID: 34478742]
[33]
Wang, J.J.; Wang, X.; Xian, Y.E.; Chen, Z.Q.; Sun, Y.P.; Fu, Y.W.; Wu, Z.K.; Li, P.X.; Zhou, E.S.; Yang, Z.T. The JMJD3 histone demethylase inhibitor GSK-J1 ameliorates lipopolysaccharide-induced inflammation in a mastitis model. J. Biol. Chem., 2022, 298(6), 102017.
[http://dx.doi.org/10.1016/j.jbc.2022.102017] [PMID: 35526564]
[34]
Johnstone, A.L.; Andrade, N.S.; Barbier, E.; Khomtchouk, B.B.; Rienas, C.A.; Lowe, K.; Van Booven, D.J.; Domi, E.; Esanov, R.; Vilca, S.; Tapocik, J.D.; Rodriguez, K.; Maryanski, D.; Keogh, M.C.; Meinhardt, M.W.; Sommer, W.H.; Heilig, M.; Zeier, Z.; Wahlestedt, C. Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways. Addict. Biol., 2021, 26(1), e12816.
[http://dx.doi.org/10.1111/adb.12816] [PMID: 31373129]
[35]
Huang, M.; Wang, Q.; Long, F.; Di, Y.; Wang, J.; Zhu, Z. Y.; Liu, X. Jmjd3 regulates inflammasome activation and aggravates DSS‐induced colitis in mice. FASEB J., 2020, 34(3), 4107-4119.
[http://dx.doi.org/10.1096/fj.201902200RR] [PMID: 31971317]
[36]
He, Z.; Wang, H.; Yue, L. Endothelial progenitor cells-secreted extracellular vesicles containing microRNA-93-5p confer protection against sepsis-induced acute kidney injury via the KDM6B/H3K27me3/TNF-α axis. Exp. Cell Res., 2020, 395(2), 112173.
[http://dx.doi.org/10.1016/j.yexcr.2020.112173] [PMID: 32679234]
[37]
Pathria, G.; Scott, D.A.; Feng, Y.; Sang Lee, J. Fujita, Y.; Zhang, G.; Sahu, A.D.; Ruppin, E.; Herlyn, M.; Osterman, A.L.; Ronai, Z.A. Targeting the Warburg effect via LDHA inhibition engages ATF 4 signaling for cancer cell survival. EMBO J., 2018, 37(20), e99735.
[http://dx.doi.org/10.15252/embj.201899735] [PMID: 30209241]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy