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Protective effect of basic alkaline ceramidase 1 in ulcerative colitis
Received date: 2024-10-30
Online published: 2025-01-14
Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis (UC). Methods Acer1 knockout mice (Acer1 KO) were constructed, and the UC model was induced by continuous drinking water of sodium dextran sulfate (DSS) for 7 days, and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared. The expression levels of intestinal mucosal barriers (ZO-1, Occludin, Claudin, JAMA) were detected by RT-PCR and immunohistochemistry. Systemic immune response levels (IL-1b、IL-6、IL-23、IL-17、IL-10, and TNF-a) were assessed by ELISA and intestinal inflammatory infiltration levels (TNF-a、IL-1b、IL-6、IL-17、IL-21, etc.) were assessed by RT-PCR. Results There was no significant difference between C57 and Acer1 KO mice in free drinking water. In the DSS induced UC model, compared with C57 mice, the survival rate of Acer1 KO mice decreased, the weight decreased significantly, the mechanical barrier and mucus barrier protein expression levels decreased significantly, the intestinal epithelial barrier was seriously damaged, the inflammatory response was strong, and the cytokine infiltration was obvious, with statistical differences (P < 0.05). Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier, preventing endotoxin, and delaying the progression of UC.
Rongmao HE , Zeyang FANG , Yunyun ZHANG , Youliang WU , Shixiu LIANG , Siqi WANG . Protective effect of basic alkaline ceramidase 1 in ulcerative colitis[J]. The Journal of Practical Medicine, 2025 , 41(1) : 7 -14 . DOI: 10.3969/j.issn.1006-5725.2025.01.002
| 1 | ANANTHAKRISHNAN A N. Epidemiology and risk factors for IBD[J]. Nat Rev Gastroenterol Hepatol, 2015, 12(4):205-217. doi:10.1038/nrgastro.2015.34 |
| 2 | KA?U?NA A, OLCZYK P, KOMOSI?SKA-VASSEV K. The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis[J]. J Clin Med, 2022, 11(2):400. doi:10.3390/jcm11020400 |
| 3 | ?WIRKOSZ G, SZCZYGIE? A, LOGO? K, et al. The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review[J]. Biomedicines, 2023, 11(12):3144. doi:10.3390/biomedicines11123144 |
| 4 | ZOU J, LIU C, JIANG S, et al. Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis[J]. Infect Immun, 2021, 89(9):e0001421. doi:10.1128/iai.00014-21 |
| 5 | WANGCHUK P, YESHI K, LOUKAS A. Ulcerative colitis: Clinical biomarkers, therapeutic targets, and emerging treatments[J]. Trends Pharmacol Sci, 2024, 45(10):892-903. doi:10.1016/j.tips.2024.08.003 |
| 6 | BIAZZO M, DEIDDA G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases[J]. J Clin Med, 2022, 11(14):4119. doi:10.3390/jcm11144119 |
| 7 | KOBAYASHI T, SIEGMUND B, LE BERRE C, et al. Ulcerative colitis[J]. Nat Rev Dis Primers, 2020, 6(1):74. doi:10.1038/s41572-020-0205-x |
| 8 | PAI R K, D'HAENS G, KOBAYASHI T, et al. Histologic assessments in ulcerative colitis: The evidence behind a new endpoint in clinical trials[J]. Expert Rev Gastroenterol Hepatol, 2024, 18(1/3):73-87. doi:10.1080/17474124.2024.2326838 |
| 9 | NEURATH M F, VIETH M. Different levels of healing in inflammatory bowel diseases: Mucosal, histological, transmural, barrier and complete healing[J]. Gut,2023, 72(11):2164-2183. doi:10.1136/gutjnl-2023-329964 |
| 10 | MORIICHI K, FUJIYA M, OKUMURA T. The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease[J]. Dig Endosc,2021, 33(7):1008-1023. doi:10.1111/den.13863 |
| 11 | YAMAMOTO-FURUSHO J K, MARTíNEZ-BENíTEZ B, SáNCHEZ-MORALES G E. Histopathologic parameters at diagnosis as early predictors of histologic remission along the course of ulcerative colitis[J]. Gastroenterol Res Pract, 2020, 2020:8891937. doi:10.1155/2020/8891937 |
| 12 | HUANG L, HE F, WU B. Mechanism of effects of nickel or nickel compounds on intestinal mucosal barrier[J]. Chemosphere, 2022, 305:135429. doi:10.1016/j.chemosphere.2022.135429 |
| 13 | LI Y Y, WANG X J, SU Y L, et al. Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s[J]. Acta Pharmacol Sin, 2022, 43(6):1495-1507. doi:10.1038/s41401-021-00781-7 |
| 14 | ZHOU Z, GUO K, LUO Y, et al. Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles[J]. Theranostics, 2024, 14(2):528-546. doi:10.7150/thno.87739 |
| 15 | FAN X, ZHANG Z, GAO W, et al. An engineered butyrate-derived polymer nanoplatform as a mucosa-healing enhancer potentiates the therapeutic effect of magnolol in inflammatory bowel disease[J]. ACS Nano, 2024, 18(1):229-244. doi:10.1021/acsnano.3c05732 |
| 16 | COANT N, SAKAMOTO W, MAO C, et al. Ceramidases, roles in sphingolipid metabolism and in health and disease[J]. Adv Biol Regul, 2017, 63:122-131. doi:10.1016/j.jbior.2016.10.002 |
| 17 | LIU Z, YANG X, CHEN S, et al. Tumor suppressor ACER1 correlates with prognosis and immune infiltration in head and neck squamous cell carcinoma[J]. Sci Rep, 2024, 14(1):28039. doi:10.1038/s41598-024-78663-1 |
| 18 | ZHANG X, GONG Z, SHEN Y, et al. Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation[J]. Nat Cardiovasc Res, 2023, 2(12):1173-1189. doi:10.1038/s44161-023-00364-1 |
| 19 | NYSTR?M N, PRAST-NIELSEN S, CORREIA M, et al. Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers[J]. J Crohns Colitis, 2023, 17(3):418-432. doi:10.1093/ecco-jcc/jjac149 |
| 20 | KAPLAN G G. The global burden of IBD: from 2015 to 2025[J]. Nat Rev Gastroenterol Hepatol, 2015, 12(12):720-727. doi:10.1038/nrgastro.2015.150 |
| 21 | DI SABATINO A, SANTACROCE G, ROSSI C M, et al. Role of mucosal immunity and epithelial-vascular barrier in modulating gut homeostasis[J]. Intern Emerg Med, 2023, 18(6):1635-1646. doi:10.1007/s11739-023-03329-1 |
| 22 | WANG J, HE M, YANG M, et al. Gut microbiota as a key regulator of intestinal mucosal immunity[J]. Life Sci, 2024, 345:122612. doi:10.1016/j.lfs.2024.122612 |
| 23 | WOLLNY T, W?TEK M, DURNA? B, et al. Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease[J]. Int J Mol Sci, 2017, 18(4):741. doi:10.3390/ijms18040741 |
| 24 | KIHARA A. Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides[J]. Prog Lipid Res, 2016, 63:50-69. doi:10.1016/j.plipres.2016.04.001 |
| 25 | DU Y X, ZHAO Y T, SUN Y X, et al. Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis[J]. Mol Med, 2023, 29(1):125. doi:10.1186/s10020-023-00724-4 |
| 26 | MACEYKA M, SPIEGEL S. Sphingolipid metabolites in inflammatory disease[J]. Nature, 2014, 510(7503):58-67. doi:10.1038/nature13475 |
| 27 | BOCK J, LIEBISCH G, SCHWEIMER J, et al. Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function[J]. World J Gastroenterol, 2007, 13(39):5217-5225. doi:10.3748/wjg.v13.i39.5217 |
| 28 | LIAKATH-ALI K, VANCOLLIE V E, LELLIOTT C J, et al. Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole-body energy expenditure[J]. J Pathol, 2016, 239(3):374-383. doi:10.1002/path.4737 |
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