Abstract
This experiment successfully isolated the rat colonic epithelial cells and established a TNF-α-induced intestinal inflammation model. Western Blot was used to detect the related protein expression levels of the MAPKs signaling pathway. QPCR technology was used to detect the expression of aquaporins, intestinal mucosal repair factor, and inflammatory factors. The results show that 25 μM β-carotene pretreatment at 24 h can inhibit MAPKs signaling pathway activated by TNF-α, change the relative mRNA expression of inflammatory cytokines, intestinal mucosal repair factors, and aquaporins, and the phosphorylated protein expression of p38, ERK, and NF-κB were attenuated to reduce inflammatory damage. After inhibiting p38 and ERK, the effect of β-carotene was reduced significantly (P < 0.05). In conclusion, β-carotene can alleviate the abnormal expression of aquaporins caused by inflammation through the MAPKs signaling pathway. This is for β-carotene as a functional nutrient that provides new insights.
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References
Quadro, L., Giordano, E., Costabile, B. K., Nargis, T., Iqbal, J., Kim, Y., Wassef, L., & Hussain, M. M. (2020). Interplay between beta-carotene and lipoprotein metabolism at the maternal-fetal barrier. Biochimica et Biophysica Acta, Molecular Cell Research, 1865, 158591.
Qian, C., Decker, E. A., Xiao, H., & McClements, D. J. (2012). Physical and chemical stability of beta-carotene-enriched nanoemulsions: Influence of pH, ionic strength, temperature, and emulsifier type. Food Chem, 132, 1221–1229.
Grar, H., Dib, W., Gourine, H., Negaoui, H., Taleb, B. H. F., Louaar, A., Ouldhocine, S., Kaddouri, H., Kheroua, O., & Saidi, D. (2020). β-Carotene improves intestinal barrier function by modulating proinflammatory cytokines and improving antioxidant capacity in β-lactoglobulin-sensitized mice. Journal of Biological Regulators and Homeostatic Agents, 34, 1689–1697.
Hardin, J. A., Wallace, L. E., Wong, J. F., O’Loughlin, E. V., Urbanski, S. J., Gall, D. G., MacNaughton, W. K., & Beck, P. L. (2004). Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn’s disease and infectious colitis. Cell Tissue Res, 318, 313–323.
Zhao, G., Li, J., Wang, J., Shen, X., & Sun, J. (2014). Aquaporin 3 and 8 are down-regulated in TNBS-induced rat colitis. Biochemical and Biophysical Research Communications, 443, 161–166.
Ricanek, P., Lunde, L. K., Frye, S. A., Støen, M., Nygård, S., Morth, J. P., Rydning, A., Vatn, M. H., Amiry-Moghaddam, M., & Tønjum, T. (2015). Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease. Clinical and Experimental Gastroenterology, 8, 49–67.
Sisto, M., Ribatti, D., & Lisi, S. (2019). Aquaporin water channels: new perspectives on the potential role in inflammation. Advances in Protein Chemistry and Structural Biology, 116, 311–345.
Maidhof, R., Jacobsen, T., Papatheodorou, A., & Chahine, N. O. (2014). Inflammation induces irreversible biophysical changes in isolated nucleus pulposus cells. PLoS One, 9, e99621.
Baud, V., & Karin, M. (2001). Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biology, 11, 372–377.
Nagahara, M., Waguri-Nagaya, Y., Yamagami, T., Aoyama, M., Tada, T., Inoue, K., Asai, K., & Otsuka, T. (2010). TNF-alpha-induced aquaporin 9 in synoviocytes from patients with OA and RA. Rheumatology (Oxford), 49, 898–906.
Fang, J. Y., & Richardson, B. C. (2005). The MAPK signalling pathways and colorectal cancer. The Lancet Oncology, 6, 322–327.
Dong, C., Davis, R. J., & Flavell, R. A. (2002). MAP kinases in the immune response. Annual Review of Immunology, 20, 55–72.
Chen, D. B., & Davis, J. S. (2003). Epidermal growth factor induces c-fos and c-jun mRNA via Raf-1/MEK1/ERK-dependent and -independent pathways in bovine luteal cells. Molecular and Cellular Endocrinology, 200, 141–154.
Lee, J. C., Laydon, J. T., McDonnell, P. C., Gallagher, T. F., Kumar, S., Green, D., McNulty, D., Blumenthal, M. J., Heys, J. R., Landvatter, S. W., Strickler, J. E., McLaughlin, M. M., Siemens, I. R., Fisher, S. M., Livi, G. P., White, J. R., Adams, J. L., & Young, P. R. (1994). A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372, 739–746.
Pearson, G., Robinson, F., Beers Gibson, T., Xu, B. E., Karandikar, M., Berman, K., & Cobb, M. H. (2001). Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews, 22, 153–183.
Carter, A. B., Knudtson, K. L., Monick, M. M., & Hunninghake, G. W. (1999). The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). Journal of Biological Chemistry, 274, 30858–30863.
Schindler, J. F., Monahan, J. B., & Smith, W. G. (2007). p38 pathway kinases as anti-inflammatory drug targets. Journal of Dental Research, 86, 800–811.
Underwood, D. C., Osborn, R. R., Bochnowicz, S., Webb, E. F., Rieman, D. J., Lee, J. C., Romanic, A. M., Adams, J. L., Hay, D. W., & Griswold, D. E. (2000). SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279, L895–902.
Badger, A. M., Bradbeer, J. N., Votta, B., Lee, J. C., Adams, J. L., & Griswold, D. E. (1996). Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. Journal of Pharmacology and Experimental Therapeutics., 279, 1453–1461.
Wadsworth, S. A., Cavender, D. E., Beers, S. A., Lalan, P., Schafer, P. H., Malloy, E. A., Wu, W., Fahmy, B., Olini, G. C., Davis, J. E., Pellegrino-Gensey, J. L., Wachter, M. P., & Siekierka, J. J. (1999). RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. Journal of Pharmacology and Experimental Therapeutics, 291, 680–687.
Zhao, W. X., Cui, N., Jiang, H. Q., Ji, X. M., Han, X. C., Han, B. B., Wang, T., & Wang, S. J. (2017). Effects of radix astragali and its split components on gene expression profiles related to water metabolism in rats with the dampness stagnancy due to spleen deficiency syndrome. Evidence-Based Complementary and Alternative Medicine, 2017, 4946031.
Chen, J., Li, Y., Tian, Y., Huang, C., Li, D., Zhong, Q., & Ma, X. (2015). Interaction between microbes and host intestinal health: modulation by dietary nutrients and gut-brain-endocrine-immune axis. Current Protein & Peptide Science, 16, 592–603.
Fan, P., Li, L., Rezaei, A., Eslamfam, S., Che, D., & Ma, X. (2015). Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Current Protein & Peptide Science, 16, 646–654.
Zhu, L., Cai, X., Guo, Q., Chen, X., Zhu, S., & Xu, J. (2013). Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways’ response to oxidative stress in weaned piglets. British Journal of Nutrition, 110, 1938–1947.
Modina, S. C., Polito, U., Rossi, R., Corino, C., & Di Giancamillo, A. (2019). Nutritional regulation of gut barrier integrity in weaning piglets. Animals (Basel), 2019, 9.
Oswald, I. P. (2006). Role of intestinal epithelial cells in the innate immune defence of the pig intestine. Veterinary Research, 37, 359–368.
Johansson, M. E., Sjövall, H., & Hansson, G. C. (2013). The gastrointestinal mucus system in health and disease. Nature Reviews Gastroenterology & Hepatology, 10, 352–361.
Baud, V., & Derudder, E. (2011). Control of NF-κB activity by proteolysis. Current Topics in Microbiology and Immunology, 349, 97–114.
Lauridsen, C. (2019). From oxidative stress to inflammation: redox balance and immune system. Poultry Science, 98, 4240–4246.
Cassidy, H., Radford, R., Slyne, J., O’Connell, S., Slattery, C., Ryan, M. P., & McMorrow, T. (2012). The role of MAPK in drug-induced kidney injury. Journal of Signal Transduction, 2012, 463617.
Wan, F., & Lenardo, M. J. (2010). The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives. Cell Research, 20, 24–33.
Umenishi, F., & Schrier, R. W. (2002). Identification and characterization of a novel hypertonicity-responsive element in the human aquaporin-1 gene. Biochemical and Biophysical Research Communications, 292, 771–775.
Umenishi, F., & Schrier, R. W. (2003). Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. Journal of Biological Chemistry, 278, 15765–15770.
Umenishi, F., Narikiyo, T., & Schrier, R. W. (2004). Hypertonic induction of aquaporin-1 water channel independent of transcellular osmotic gradient. Biochemical and Biophysical Research Communications, 325, 595–599.
Zhao, G. X., Dong, P. P., Peng, R., Li, J., Zhang, D. Y., Wang, J. Y., Shen, X. Z., Dong, L., & Sun, J. Y. (2016). Expression, localization and possible functions of aquaporins 3 and 8 in rat digestive system. Biotechnic & Histochemistry, 91, 269–276.
Matsuura, M., Okazaki, K., Nishio, A., Nakase, H., Tamaki, H., Uchida, K., Nishi, T., Asada, M., Kawasaki, K., Fukui, T., Yoshizawa, H., Ohashi, S., Inoue, S., Kawanami, C., Hiai, H., Tabata, Y., & Chiba, T. (2005). Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis. Gastroenterology, 128, 975–986.
Galura, G. M., Chavez, L. O., Robles, A., & McCallum, R. (2019). Gastroduodenal injury: role of protective factors. Curr Gastroenterology Report, 21, 34.
Tang, X., Ma, W., Zhan, W., Wang, X., Dong, H., Zhao, H., Yang, L., Ji, C., Han, Q., Ji, C., Liu, H., & Wang, N. (2018). Internal biliary drainage superior to external biliary drainage in improving gut mucosa barrier because of goblet cells and mucin-2 up-regulation. Bioscience Report, 2018, 38.
Zhang, S., Xu, W., Wang, H., Cao, M., Li, M., Zhao, J., Hu, Y., Wang, Y., Li, S., Xie, Y., Chen, G., Liu, R., Cheng, Y., Xu, Z., Zou, K., Gong, S. & & Geng, L. (2019). Inhibition of CREB-mediated ZO-1 and activation of NF-kappaB-induced IL-6 by colonic epithelial MCT4 destroys intestinal barrier function. Cell Proliferation, 52, e12673
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This work was supported by the National Natural Science Foundation of China (31672511).
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YS and LZ co-designed the study and wrote the manuscript. All authors contributed to the article and approved the submitted version.
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This experiment was approved by the Animal Ethical Committee of Jilin Agricultural University (no. 201705001).
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Song, Y., Zhu, L. & Zheng, X. β-carotene inhibits MAPKs signaling pathways on rat colonic epithelial cells to attenuate TNF-α-induced intestinal inflammation and injury. Cell Biochem Biophys 82, 291–302 (2024). https://doi.org/10.1007/s12013-023-01202-8
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DOI: https://doi.org/10.1007/s12013-023-01202-8