Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Medicine
  4. Volume 25, Issue 3
  5. Article
Volume 25, Issue 3
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Objective

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear.

Materials and Methods

The and models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays.

Results

MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR-146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC.

Conclusion

MiR-146a knockdown inhibited cell apoptosis and inflammation targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240273807231122052445
2025-03-01
2025-05-11

  • From This Site

    /content/journals/cmm/10.2174/0115665240273807231122052445
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. LeyD LeroyerA DupontC New therapeutic strategies are associated with a significant decrease in colectomy rate in pediatric ulcerative colitis.Am J Gastroenterol 2023; Publish Ahead of Print10.14309/ajg.000000000000231637141541
  2. DoH. KimY. OhT. Aureobasidium pullulansEffect of polycan, a β-Glucan from SM-2001, on inflammatory response and intestinal barrier function in dss-induced ulcerative colitis.Int. J. Mol. Sci.2023241910.3390/ijms241914773 37834221
     [Google Scholar]
  3. LiF. YangY. GeJ. Multi-omics revealed the mechanisms of Codonopsis pilosula aqueous extract in improving UC through blocking abnormal activation of PI3K/Akt signaling pathway.J. Ethnopharmacol.2023319Pt 2117220 37820998
     [Google Scholar]
  4. YiJ. BergstromK. FuJ. Dclk1 in tuft cells promotes inflammation-driven epithelial restitution and mitigates chronic colitis.Cell Death Differ.20192691656166910.1038/s41418‑018‑0237‑x 30478383
     [Google Scholar]
  5. HeazlewoodC.K. CookM.C. EriR. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.PLoS Med.200853e5410.1371/journal.pmed.0050054 18318598
     [Google Scholar]
  6. AtreyaR. NeurathM.F. Induction of microRNA-124 as a novel therapeutic concept in ulcerative colitis.Lancet Gastroenterol. Hepatol.202271197797810.1016/S2468‑1253(22)00249‑7 36075248
     [Google Scholar]
  7. DhupparS. MurugaiyanG. miRNA effects on gut homeostasis: Therapeutic implications for inflammatory bowel disease.Trends Immunol.2022431191793110.1016/j.it.2022.09.003 36220689
     [Google Scholar]
  8. JimenezM.T. ClarkM.L. WrightJ.M. The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium.J. Exp. Med.202221912e2021227810.1084/jem.20212278 36074090
     [Google Scholar]
  9. WangX. ZhangD. YangY. Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.Front. Immunol.202314108980910.3389/fimmu.2023.1089809 36776858
     [Google Scholar]
  10. HeC. ChenZ. HuangJ. Interleukin-22 ameliorates dextran sulfate sodium-induced colitis through the upregulation of lncrna-ucl to accelerate Claudin-1 expression via sequestering miR-568 in mice.Oxid. Med. Cell. Longev.2022202211810.1155/2022/8543720 36092152
     [Google Scholar]
  11. KoukosG. PolytarchouC. KaplanJ.L. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis.Gastroenterology20131454842852.e210.1053/j.gastro.2013.07.001 23856509
     [Google Scholar]
  12. MinM. PengL. YangY. GuoM. WangW. SunG. MicroRNA-155 is involved in the pathogenesis of ulcerative colitis by targeting FOXO3a.Inflamm. Bowel Dis.201420465265910.1097/MIB.0000000000000009 24583476
     [Google Scholar]
  13. XiaF. BoW. DingJ. YuY. WangJ. MiR-222-3p aggravates the inflammatory response by targeting SOCS1 to activate STAT3 signaling in ulcerative colitis.Turk. J. Gastroenterol.20223311934944
     [Google Scholar]
  14. ChithanathanK. JürgensonM. GuhaM. Paradoxical attenuation of neuroinflammatory response upon LPS challenge in miR-146b deficient mice.Front. Immunol.20221399641510.3389/fimmu.2022.996415 36389659
     [Google Scholar]
  15. JiangC. LinY. ShanH. Staphylococcus aureusmiR-146a protects against -induced osteomyelitis by regulating inflammation and osteogenesis.ACS Infect. Dis.20228591892710.1021/acsinfecdis.1c00459 35410468
     [Google Scholar]
  16. LaanesooA. UrgardE. PeriyasamyK. Dual role of the miR‐146 family in rhinovirus‐induced airway inflammation and allergic asthma exacerbation.Clin. Transl. Med.2021116e42710.1002/ctm2.427 34185416
     [Google Scholar]
  17. BaoS.Y. SunQ.X. YaoC.L. The interaction of TAK1 and TAB1 enhances LPS-induced cytokine release via modulating NF-κB activation (Larimichthys crocea).Fish Shellfish Immunol.20187445045810.1016/j.fsi.2018.01.005 29325713
     [Google Scholar]
  18. OhkawaraB. ShirakabeK. Hyodo-MiuraJ. Role of the TAK1-NLK-STAT3 pathway in TGF-β-mediated mesoderm induction.Genes Dev.200418438138610.1101/gad.1166904 15004007
     [Google Scholar]
  19. LiuX. LiH. ZhongB. USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1–TAB1 complex.J. Exp. Med.201321081575159010.1084/jem.20122327 23825189
     [Google Scholar]
  20. YangC. YangC. ZhangJ. MicroRNA-211 regulates the expression of TAB1 and inhibits the NF-κB signaling pathway in lipopolysaccharide-induced endometritis.Int. Immunopharmacol.20219610766810.1016/j.intimp.2021.107668 33984721
     [Google Scholar]
  21. GongH. FangL. LiY. miR 873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and TAB1.Oncol. Rep.20183931090109810.3892/or.2018.6199 29328486
     [Google Scholar]
  22. LoddenkemperC. Diagnostic standards in the pathology of inflammatory bowel disease.Dig. Dis.200927457658310.1159/000233301 19897978
     [Google Scholar]
  23. WangS. ShenL. LuoH. Identification and validation of key miRNAs and a microRNA-mRNA regulatory network associated with ulcerative colitis.DNA Cell Biol.202140214715610.1089/dna.2020.6151 33347387
     [Google Scholar]
  24. GaroL.P. AjayA.K. FujiwaraM. MicroRNA-146a limits tumorigenic inflammation in colorectal cancer.Nat. Commun.2021121241910.1038/s41467‑021‑22641‑y 33893298
     [Google Scholar]
  25. WangJ.P. DongL.N. WangM. GuoJ. ZhaoY.Q. MiR-146a regulates the development of ulcerative colitis via mediating the TLR4/MyD88/NF-κB signaling pathway.Eur. Rev. Med. Pharmacol. Sci.201923521512157 30915760
     [Google Scholar]
  26. CuiJ. ZhengW. SunY. XuT. Inducible MicroRNA-132 inhibits the production of inflammatory cytokines by targeting TRAF6, TAK1, and TAB1 in teleost fish.Infect. Immun.2022905e001202210.1128/iai.00120‑22 35416706
     [Google Scholar]
  27. KozyckiC.T. KodatiS. HurynL. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.Ann. Rheum. Dis.202281101453146410.1136/annrheumdis‑2022‑222629 35868845
     [Google Scholar]
  28. HeZ. SongQ. YuY. Protein therapy of skeletal muscle atrophy and mechanism by angiogenic factor AGGF1.J. Cachexia Sarcopenia Muscle202314297899110.1002/jcsm.13179 36696895
     [Google Scholar]
  29. YaoD. ZhouZ. WangP. MiR-125-5p/IL-6R axis regulates macrophage inflammatory response and intestinal epithelial cell apoptosis in ulcerative colitis through JAK1/STAT3 and NF-κB pathway.Cell Cycle202120232547256410.1080/15384101.2021.1995128 34747340
     [Google Scholar]
  30. ZengJ. ZhangD. WanX. Chlorogenic acid suppresses miR‐155 and ameliorates ulcerative colitis through the NF‐κB/NLRP3 inflammasome pathway.Mol. Nutr. Food Res.20206423200045210.1002/mnfr.202000452 33078870
     [Google Scholar]
  31. LuX. YuY. TanS. The role of the miR-21-5p-mediated inflammatory pathway in ulcerative colitis.Exp. Ther. Med.2020192981989 32010260
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240273807231122052445
Loading
Explore on the Mechanism of miRNA-146a/TAB1 in the Regulation of Cellular Apoptosis and Inflammation in Ulcerative Colitis Based on NF-κB Pathway
Current Molecular Medicine 25, 330 (2025); https://doi.org/10.2174/0115665240273807231122052445
/content/journals/cmm/10.2174/0115665240273807231122052445
/content/journals/cmm/10.2174/0115665240273807231122052445
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): apoptosis; inflammation; miR-146a; NF-kB pathway; TAB1; Ulcerative colitis

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test