Academic Journal
Coal Dust-Mimetic Carbon Nanoparticles Induce Colonic Epithelial Cell Senescence via p16/p21 Dual Pathways and Promote Colonic Inflammatory Response.
| Τίτλος: | Coal Dust-Mimetic Carbon Nanoparticles Induce Colonic Epithelial Cell Senescence via p16/p21 Dual Pathways and Promote Colonic Inflammatory Response. |
|---|---|
| Συγγραφείς: | Wang Y; The First Hospital of Anhui University of Science and Technology, Huainan, China., Zhang C; Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, China., Li X; The First Hospital of Anhui University of Science and Technology, Huainan, China., Li S; The First Hospital of Anhui University of Science and Technology, Huainan, China., Jiang W; The First Hospital of Anhui University of Science and Technology, Huainan, China., Duan B; The First Hospital of Anhui University of Science and Technology, Huainan, China., Liu X; The First Hospital of Anhui University of Science and Technology, Huainan, China., Zhou S; The First Hospital of Anhui University of Science and Technology, Huainan, China., Zhang Y; The First Hospital of Anhui University of Science and Technology, Huainan, China. |
| Πηγή: | Journal of gastroenterology and hepatology [J Gastroenterol Hepatol] 2026 Aug; Vol. 41 (8), pp. 2374-2392. Date of Electronic Publication: 2026 Jun 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Blackwell Scientific Publications Country of Publication: Australia NLM ID: 8607909 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1746 (Electronic) Linking ISSN: 08159319 NLM ISO Abbreviation: J Gastroenterol Hepatol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Melbourne ; Boston : Blackwell Scientific Publications, c1986- |
| Ιατρικοί όροι (MeSH): | Cellular Senescence*/drug effects , Cellular Senescence*/genetics , Nanoparticles*/adverse effects , Nanoparticles*/toxicity , Carbon*/toxicity , Carbon*/adverse effects , Signal Transduction*/genetics , Signal Transduction*/physiology , Signal Transduction*/drug effects , Cyclin-Dependent Kinase Inhibitor p21*/metabolism , Cyclin-Dependent Kinase Inhibitor p16*/metabolism , Coal*/adverse effects , Coal*/toxicity , Epithelial Cells*/pathology , Colon*/pathology , Colon*/cytology , Inflammatory Bowel Diseases*/etiology , Inflammatory Bowel Diseases*/pathology , Dust*, Mitochondria/pathology ; Reactive Oxygen Species/metabolism ; Animals ; Male ; Intestinal Barrier Function ; Disease Models, Animal ; Carbon Nanomaterials ; Gastrointestinal Microbiome |
| Περίληψη: | Background and Aim: The incidence of inflammatory bowel disease among coal miners is globally higher than that in the general population; however, the underlying pathogenic mechanisms remain unclear. Given that the composition and particle size of coal dust are key determinants of its toxicity, this study investigates the pathogenic role and molecular mechanism of coal dust-mimetic carbon nanoparticles (CNPs) in inflammatory bowel disease. Methods: In this study, an in vivo exposure rat model was established by intranasal instillation of CNPs for 4, 8, and 12 weeks. Combined with transcriptomic sequencing as well as in vivo and in vitro experiments, relevant indicators of mitochondrial damage and cellular senescence were systematically evaluated. Results: Rats intranasally administered with CNPs exhibited sustained decreases in daily weight gain, elevated spleen index, along with colonic pathological damage, inflammatory responses, impaired intestinal barrier function, and gut microbiota dysbiosis. Furthermore, in vitro and in vivo, incorporating transcriptomic sequencing and experimental research have confirmed that CNP exposure induces mitochondrial damage, evident from enriched mitochondrial damage signals, altered mitochondrial morphology and structure, increased reactive oxygen species levels, and reduced mitochondrial membrane potential. Simultaneously, cellular senescence is triggered, including cell cycle arrest, suppressed transcriptional activity, reduced cell proliferation capacity, and marked activation of the p16/p21 dual signaling pathway. Conclusions: These findings suggest that the simultaneous enrichment of mitochondrial damage signals and cellular senescence phenotypes may be a core event in CNP-induced colitis, with the p16/p21 dual signal acting as the "molecular switch" regulating this process. Targeting and inhibiting the p16/p21 dual signaling pathway may offer a novel strategy for preventing and treating colitis induced by coal dust exposure in coal miners. (© 2026 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.) |
| References: | Data Brief. 2022 Apr 01;42:108125. (PMID: 35496476) Nat Rev Microbiol. 2025 Aug;23(8):509-524. (PMID: 40065181) Nanotoxicology. 2010 Mar;4(1):120-37. (PMID: 20795906) Toxicol Ind Health. 2020 Mar;36(3):181-213. (PMID: 32539642) Front Cell Dev Biol. 2020 Oct 23;8:588836. (PMID: 33195251) Biochem J. 2002 Sep 1;366(Pt 2):613-21. (PMID: 11945174) Cell Death Discov. 2022 Dec 29;8(1):500. (PMID: 36581638) Toxicol Ind Health. 2019 Oct;35(10):627-637. (PMID: 31694480) Gut Microbes. 2024 Jan-Dec;16(1):2420765. (PMID: 39462280) J Appl Toxicol. 2022 Jul;42(7):1098-1120. (PMID: 34935166) J Clin Invest. 2022 Jul 1;132(13):. (PMID: 35775483) Nature. 2020 Oct;586(7829):434-439. (PMID: 33029007) Cochrane Database Syst Rev. 2021 Nov 29;11:CD013531. (PMID: 34844288) ACS Nano. 2025 Aug 12;19(31):28242-28256. (PMID: 40719097) Ecotoxicol Environ Saf. 2015 Oct;120:155-62. (PMID: 26072196) Probiotics Antimicrob Proteins. 2022 Aug;14(4):648-663. (PMID: 34985682) BMC Microbiol. 2019 Nov 6;19(1):246. (PMID: 31694526) Trends Biotechnol. 2015 Sep;33(9):496-503. (PMID: 26210164) Environ Int. 2023 Jun;176:107968. (PMID: 37201399) Ecotoxicol Environ Saf. 2019 Oct 30;182:109439. (PMID: 31306920) Nihon Eiseigaku Zasshi. 2015;70(2):127-33. (PMID: 25994344) Prim Care. 2023 Sep;50(3):411-427. (PMID: 37516511) Nature. 2022 Nov;611(7937):801-809. (PMID: 36266581) Gastroenterology. 2024 Jan;166(1):44-58. (PMID: 37734419) Clin Gastroenterol Hepatol. 2023 Dec;21(13):3379-3386.e29. (PMID: 37660767) Eur J Pharm Sci. 2025 Jun 1;209:107098. (PMID: 40216167) Sci Adv. 2023 May 24;9(21):eadg3683. (PMID: 37224246) Arch Toxicol. 2020 May;94(5):1479-1495. (PMID: 32180035) Int Immunopharmacol. 2024 Nov 15;141:112810. (PMID: 39151382) World J Gastroenterol. 2014 Jan 7;20(1):91-9. (PMID: 24415861) Respir Res. 2022 Jul 30;23(1):197. (PMID: 35906696) Nat Commun. 2019 Jan 3;10(1):38. (PMID: 30604764) Int J Mol Sci. 2022 Jun 21;23(13):. (PMID: 35805905) Front Microbiol. 2023 Jan 12;13:1103836. (PMID: 36713166) Int J Biol Macromol. 2018 Feb;107(Pt A):1278-1293. (PMID: 29017884) Ecotoxicol Environ Saf. 2024 Apr 1;274:116214. (PMID: 38489907) Acta Pharmacol Sin. 2022 Jun;43(6):1495-1507. (PMID: 34671110) United European Gastroenterol J. 2022 Dec;10(10):1047-1053. (PMID: 36262056) Gut Microbes. 2020 Nov 9;12(1):1-14. (PMID: 32897773) ACS Nano. 2024 Jan 9;18(1):229-244. (PMID: 38112525) Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7. (PMID: 26323879) Science. 2019 Jun 21;364(6446):1179-1184. (PMID: 31221858) J Breath Res. 2021 Sep 27;15(4):. (PMID: 34507310) J Korean Med Sci. 2024 Aug 05;39(30):e227. (PMID: 39106890) Gut. 2020 Nov;69(11):1939-1951. (PMID: 32111634) Reprod Toxicol. 2015 Aug 15;56:118-40. (PMID: 26050605) Environ Health Perspect. 2005 Jul;113(7):823-39. (PMID: 16002369) |
| Grant Information: | 202427b10020071 Clinical and Translational Research Project of Anhui Province; 202304295107020036 Clinical and Translational Research Project of Anhui Province |
| Contributed Indexing: | Keywords: cellular senescence; coal dust‐mimetic carbon nanoparticles; gut microbiota; inflammatory bowel disease; mitochondrial damage; p16/p21 dual signaling pathway |
| Substance Nomenclature: | 7440-44-0 (Carbon) 0 (Cyclin-Dependent Kinase Inhibitor p21) 0 (Cyclin-Dependent Kinase Inhibitor p16) 0 (Coal) 0 (Dust) 0 (Reactive Oxygen Species) |
| Entry Date(s): | Date Created: 20260625 Date Completed: 20260803 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13431698 |
| DOI: | 10.1111/jgh.70480 |
| PMID: | 42350080 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1440-1746 |
|---|---|
| DOI: | 10.1111/jgh.70480 |