Circadian rhythm disruption modulates enteric neural precursor cells differentiation leading to gastrointestinal motility dysfunction via the NR1D1/NF-κB axis.
Animals
Gastrointestinal Motility
Cell Differentiation
Enteric Nervous System
/ pathology
Neural Stem Cells
/ metabolism
NF-kappa B
/ metabolism
Circadian Rhythm
/ physiology
Nuclear Receptor Subfamily 1, Group D, Member 1
/ metabolism
Mice, Transgenic
Signal Transduction
Mice, Inbred C57BL
Male
Mice
Circadian rhythm
Enteric nervous system
Enteric neural precursor cells
Gastrointestinal motility
NF-κB signaling
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
27
02
2024
accepted:
15
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Circadian rhythm disruption (CRD) is implicated with numerous gastrointestinal motility diseases, with the enteric nervous system (ENS) taking main responsibility for the coordination of gastrointestinal motility. The purpose of this study is to explore the role of circadian rhythms in ENS remodeling and to further elucidate the underlying mechanisms. First, we established a jet-lagged mice model by advancing the light/dark phase shift by six hours every three days for eight weeks. Subsequent changes in gastrointestinal motility and the ENS were then assessed. Additionally, a triple-transgenic mouse strain (Nestin-creER Compared to the control group, CRD significantly accelerated gastrointestinal motility, evidenced by faster intestinal peristalsis (P < 0.01), increased fecal output (P < 0.01), and elevated fecal water content (P < 0.05), as well as enhanced electrical field stimulation induced contractions (P < 0.05). These effects were associated with an increase in the number of glial cells and nitrergic neurons in the colonic myenteric plexus. Additionally, ENPCs in the colon showed a heightened differentiation into glial cells and nitrergic neurons. Notably, the NR1D1/nuclear factor-kappaB (NF-κB) axis played a crucial role in the CRD-mediated changes in ENPCs differentiation. Supplementation with NR1D1 agonist or NF-κB antagonist was able to restore gastrointestinal motility and normalize the ENS in jet-lagged mice. CRD regulates the differentiation of ENPCs through the NR1D1/NF-κB axis, resulting in dysfunction of the ENS and impaired gastrointestinal motility in mice.
Identifiants
pubmed: 39468593
doi: 10.1186/s12967-024-05766-8
pii: 10.1186/s12967-024-05766-8
doi:
Substances chimiques
NF-kappa B
0
Nuclear Receptor Subfamily 1, Group D, Member 1
0
Nr1d1 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
975Subventions
Organisme : National Natural Science Foundation of China
ID : 82100569
Organisme : National Natural Science Foundation of China
ID : 82300616
Organisme : National Natural Science Foundation of China
ID : 81974068
Organisme : National Natural Science Foundation of China
ID : 81770539
Organisme : Natural Science Foundation of Hubei Province
ID : 2023AFB301
Informations de copyright
© 2024. The Author(s).
Références
Fagiani F, Di Marino D, Romagnoli A, Travelli C, Voltan D, Di Cesare Mannelli L, Racchi M, Govoni S, Lanni C. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther. 2022;7(1):41.
doi: 10.1038/s41392-022-00899-y
pubmed: 35136018
pmcid: 8825842
Guan D, Lazar MA. Interconnections between circadian clocks and metabolism. J Clin Investig 2021, 131(15).
Fishbein AB, Knutson KL, Zee PC. Circadian disruption and human health. J Clin Investig 2021, 131(19).
Schrader LA, Ronnekleiv-Kelly SM, Hogenesch JB, Bradfield CA, Malecki KM. Circadian disruption, clock genes, and metabolic health. J Clin Investig 2024, 134(14).
Bishehsari F, Voigt RM, Keshavarzian A. Circadian rhythms and the gut microbiota: from the metabolic syndrome to cancer. Nat Rev Endocrinol. 2020;16(12):731–9.
doi: 10.1038/s41574-020-00427-4
pubmed: 33106657
pmcid: 8085809
Salgado-Delgado RC, Espinosa-Tanguma R, Valdés Abadía B, Ramírez-Plascencia OD, Escobar C, Saderi N. Feeding during the resting phase causes gastrointestinal tract dysfunction and desynchronization of metabolic and neuronal rhythms in rats. Neurogastroenterol Motil. 2023;35(12):e14687.
doi: 10.1111/nmo.14687
pubmed: 37815021
Chang WP, Peng YX. Differences between fixed day shift workers and rotating shift workers in gastrointestinal problems: a systematic review and meta-analysis. Ind Health. 2021;59(2):66–77.
doi: 10.2486/indhealth.2020-0153
pubmed: 33408309
pmcid: 8010167
Nojkov B, Rubenstein JH, Chey WD, Hoogerwerf WA. The impact of rotating shift work on the prevalence of irritable bowel syndrome in nurses. Am J Gastroenterol. 2010;105(4):842–7.
doi: 10.1038/ajg.2010.48
pubmed: 20160712
pmcid: 2887235
Chen HT, Chuang HY, Hsieh TY, Wu PS, Lin FJ, Huang HC, Yang CC, Kuo CH. Shift work is significantly and positively associated with possible gastro-esophageal reflux disease: a meta-analysis study. Front Public Health. 2022;10:980603.
doi: 10.3389/fpubh.2022.980603
pubmed: 36504996
pmcid: 9732673
Sharkey KA, Mawe GM. The enteric nervous system. Physiol Rev. 2023;103(2):1487–564.
doi: 10.1152/physrev.00018.2022
pubmed: 36521049
Holland AM, Bon-Frauches AC, Keszthelyi D, Melotte V, Boesmans W. The enteric nervous system in gastrointestinal disease etiology. Cell Mol Life Sci. 2021;78(10):4713–33.
doi: 10.1007/s00018-021-03812-y
pubmed: 33770200
pmcid: 8195951
Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020;17(6):338–51.
doi: 10.1038/s41575-020-0271-2
pubmed: 32152479
pmcid: 7474470
Mayer EA, Ryu HJ, Bhatt RR. The neurobiology of irritable bowel syndrome. Mol Psychiatry. 2023;28(4):1451–65.
doi: 10.1038/s41380-023-01972-w
pubmed: 36732586
pmcid: 10208985
Rieder E, Fernandez-Becker NQ, Sarosiek J, Guillaume A, Azagury DE, Clarke JO. Achalasia: physiology and diagnosis. Ann N Y Acad Sci. 2020;1482(1):85–94.
doi: 10.1111/nyas.14510
pubmed: 33140485
Drokhlyansky E, Smillie CS, Van Wittenberghe N, Ericsson M, Griffin GK, Eraslan G, Dionne D, Cuoco MS, Goder-Reiser MN, Sharova T, et al. The human and mouse enteric nervous system at single-cell resolution. Cell. 2020;182(6):1606–e16221623.
doi: 10.1016/j.cell.2020.08.003
pubmed: 32888429
pmcid: 8358727
Kulkarni S, Micci MA, Leser J, Shin C, Tang SC, Fu YY, Liu L, Li Q, Saha M, Li C, et al. Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc Natl Acad Sci U S A. 2017;114(18):E3709–18.
doi: 10.1073/pnas.1619406114
pubmed: 28420791
pmcid: 5422809
Yarandi SS, Kulkarni S, Saha M, Sylvia KE, Sears CL, Pasricha PJ. Intestinal Bacteria maintain adult enteric nervous system and nitrergic neurons via toll-like receptor 2-induced neurogenesis in mice. Gastroenterology. 2020;159(1):200–e213208.
doi: 10.1053/j.gastro.2020.03.050
pubmed: 32234538
Fan M, Shi H, Yao H, Wang W, Zhang Y, Jiang C, Lin R. BMSCs promote differentiation of enteric neural precursor cells to maintain neuronal homeostasis in mice with enteric nerve Injury. Cell Mol Gastroenterol Hepatol. 2023;15(2):511–31.
doi: 10.1016/j.jcmgh.2022.10.018
pubmed: 36343901
Benitah SA, Welz PS. Circadian regulation of adult stem cell homeostasis and aging. Cell Stem Cell. 2020;26(6):817–31.
doi: 10.1016/j.stem.2020.05.002
pubmed: 32502402
Gengatharan A, Malvaut S, Marymonchyk A, Ghareghani M, Snapyan M, Fischer-Sternjak J, Ninkovic J, Götz M, Saghatelyan A. Adult neural stem cell activation in mice is regulated by the day/night cycle and intracellular calcium dynamics. Cell. 2021;184(3):709–e722713.
doi: 10.1016/j.cell.2020.12.026
pubmed: 33482084
Sato S, Hishida T, Kinouchi K, Hatanaka F, Li Y, Nguyen Q, Chen Y, Wang PH, Kessenbrock K, Li W, et al. The circadian clock CRY1 regulates pluripotent stem cell identity and somatic cell reprogramming. Cell Rep. 2023;42(6):112590.
doi: 10.1016/j.celrep.2023.112590
pubmed: 37261952
Draijer S, Chaves I, Hoekman MFM. The circadian clock in adult neural stem cell maintenance. Prog Neurobiol. 2019;173:41–53.
doi: 10.1016/j.pneurobio.2018.05.007
pubmed: 29886147
Thaiss CA, Zeevi D, Levy M, Zilberman-Schapira G, Suez J, Tengeler AC, Abramson L, Katz MN, Korem T, Zmora N, et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159(3):514–29.
doi: 10.1016/j.cell.2014.09.048
pubmed: 25417104
Jin Y, Ren X, Li G, Li Y, Zhang L, Wang H, Qian W, Hou X. Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota. J Gastroenterol Hepatol. 2018;33(2):443–52.
doi: 10.1111/jgh.13841
pubmed: 28573746
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10(1):1523.
doi: 10.1038/s41467-019-09234-6
pubmed: 30944313
pmcid: 6447622
Wang S, Lin Y, Yuan X, Li F, Guo L, Wu B. REV-ERBα integrates colon clock with experimental colitis through regulation of NF-κB/NLRP3 axis. Nat Commun. 2018;9(1):4246.
doi: 10.1038/s41467-018-06568-5
pubmed: 30315268
pmcid: 6185905
Panda S, Hogenesch JB, Kay SA. Circadian rhythms from flies to human. Nature. 2002;417(6886):329–35.
doi: 10.1038/417329a
pubmed: 12015613
Seguella L, Gulbransen BD. Enteric glial biology, intercellular signalling and roles in gastrointestinal disease. Nat Rev Gastroenterol Hepatol. 2021;18(8):571–87.
doi: 10.1038/s41575-021-00423-7
pubmed: 33731961
pmcid: 8324524
McClain JL, Fried DE, Gulbransen BD. Agonist-evoked ca(2+) signaling in enteric glia drives neural programs that regulate intestinal motility in mice. Cell Mol Gastroenterol Hepatol. 2015;1(6):631–45.
doi: 10.1016/j.jcmgh.2015.08.004
pubmed: 26693173
pmcid: 4673674
Grubišić V, Gulbransen BD. Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J Physiol. 2017;595(11):3409–24.
doi: 10.1113/JP273492
pubmed: 28066889
pmcid: 5451715
Mizuta Y, Takahashi T, Owyang C. Nitrergic regulation of colonic transit in rats. Am J Physiol. 1999;277(2):G275–279.
pubmed: 10444440
Anitha M, Reichardt F, Tabatabavakili S, Nezami BG, Chassaing B, Mwangi S, Vijay-Kumar M, Gewirtz A, Srinivasan S. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice. Cell Mol Gastroenterol Hepatol. 2016;2(3):328–39.
doi: 10.1016/j.jcmgh.2015.12.008
pubmed: 27446985
pmcid: 4945127
Aubé AC, Cabarrocas J, Bauer J, Philippe D, Aubert P, Doulay F, Liblau R, Galmiche JP, Neunlist M. Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption. Gut. 2006;55(5):630–7.
doi: 10.1136/gut.2005.067595
pubmed: 16236773
pmcid: 1856141
Liu Q, Luo X, Liang Z, Qin D, Xu M, Wang M, Guo W. Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells. Proc Natl Acad Sci U S A. 2024;121(8):e2318030121.
doi: 10.1073/pnas.2318030121
pubmed: 38346182
pmcid: 10895264
Dresselhaus EC, Meffert MK. Cellular specificity of NF-κB function in the nervous system. Front Immunol. 2019;10:1043.
doi: 10.3389/fimmu.2019.01043
pubmed: 31143184
pmcid: 6520659
Xiao X, Putatunda R, Zhang Y, Soni PV, Li F, Zhang T, Xin M, Luo JJ, Bethea JR, Cheng Y, et al. Lymphotoxin β receptor-mediated NFκB signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells. J Neuroinflammation. 2018;15(1):49.
doi: 10.1186/s12974-018-1074-z
pubmed: 29463313
pmcid: 5819232
Birck C, Ginolhac A, Pavlou MAS, Michelucci A, Heuschling P, Grandbarbe L. NF-κB and TNF affect the Astrocytic differentiation from neural stem cells. Cells 2021, 10(4).
Guo DK, Zhu Y, Sun HY, Xu XY, Zhang S, Hao ZB, Wang GH, Mu CC, Ren HG. Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway. Acta Pharmacol Sin. 2019;40(1):26–34.
doi: 10.1038/s41401-018-0064-0
pubmed: 29950615