Abstract
Objective
To explore whether acupuncture combined with moxibustion could inhibit epithelialmesenchymal transition in Crohn’s disease by affecting the transforming growth factor β 1 (TGF- β 1)/Smad3/Snail pathway.
Methods
Sixty-three patients with Crohn’s disease were randomly divided into an observation group (31 cases) receiving moxibustion at 43 °C combined with acupuncture, and a control group (32 cases) receiving moxibustion at 37 °C combined with sham acupuncture using a random number table. Patients were treated for 12 weeks. Crohn’s Disease Activity Index (CDAI) was used to evaluate disease activity. Hematoxylin-eosin staining and transmission electron microscopy were utilized to observe the morphological and ultrastructural changes. Immunohistochemistry was used to detect the expression of transforming growth factor β 1 (TGF-β 1), T β R1, T β R2, Smad3, Snail, E-cadherin and fibronectin in intestinal mucosal tissues.
Results
The decrease of the CDAI score, morphological and ultrastructural changes were more significant in observation group. The expression levels of TGF- β 1, Tβ R2, Smad3, and Snail in the observation group were significantly lower than those before the treatment (P<0.05 or P<0.01). After treatment, the expression levels of TGF-β 1, TβR2, and Snail in the observation group were significantly lower than those in the control group (all P<0.05); compared with the control group, the expression of fibronectin in the observation group was significantly decreased, and the expression of E-cadherin was significantly increased (all P<0.05).
Conclusions
Moxibustion at 43 °C combined with acupuncture may suppress TGF-β 1/Smad3/Snail pathway-mediated epithelial-mesenchymal transition of intestinal epithelial cells in Crohn’s disease patients by inhibiting the expression levels of TGF-β 1, Tβ R2, Smad3, and Snail. (Registration No. ChiCTR-IIR-16007751)
Similar content being viewed by others
References
Nieto MA, Huang RY, Jackson RA, Thiery JP. EMT: 2016. Cell 2016;1:21–45.
Scharl M, Rogler G, Biedermann L. Fistulizing Crohn’s disease. Clin Transl Gastroenterol 2017;7:e106.
Latella G, Rogler G, Bamias G, Breynaert C, Florholmen J, Pellino G, et al. Results of the 4th scientific workshop of the ECCO (I): pathophysiology of intestinal fibrosis in IBD. J Crohn Colitis 2014;10:1147–1165.
Jia WX, Yang MY, Han F, Luo YX, Wu MY, Li CY, et al. Effect and mechanism of TL1A expression on epithelial-mesenchymal transition during chronic colitis-related intestinal fibrosis. Mediators Inflamm 2021;2021:5927064.
Kang E, Seo J, Yoon H, Cho S. The post-translational regulation of epithelial-mesenchymal transition-inducing transcription factors in cancer metastasis. Int J Mol Sci 2021;7:3591.
Park MJ, Lee DE, Shim MK, Jang EH, Lee JK, Jeong SY, et al. Piperlongumine inhibits TGF-beta-induced epithelial-to-mesenchymal transition by modulating the expression of E-cadherin, Snail1, and Twist1. Eur J Pharmacol 2017;812:243–249.
Baulida J, Diaz VM, Herreros AG. Snail1: a transcriptional factor controlled at multiple levels. J Clin Med 2019;6:757.
Yun SM, Kim SH, Kim EH. The molecular mechanism of transforming growth factor-beta signaling for intestinal fibrosis: a mini-review. Front Pharmacol 2019;10:162.
Shi Y, Li T, Zhou J, Li Y, Chen L, Shang H, et al. Herbs-partitioned moxibustion combined with acupuncture inhibits TGF-beta1-Smad-Snail-induced intestinal epithelial mesenchymal transition in Crohn’s disease model rats. Evid Based Complement Alternat Med 2019;2019:8320250.
Bao CH, Zhao JM, Liu HR, Lu Y, Zhu YF, Shi Y, et al. Randomized controlled trial: moxibustion and acupuncture for the treatment of Crohn’s disease. World J Gastroenterol 2014;31:11000–11011.
Singleton JW. The Crohn’s Disease Activity Index is a useful tool in clinical practice of gastroenterology. Inflamm Bowel Dis 1999;5:138–143.
Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, et al. Asia Pacific Association of Gastroenterology (APAGE) Working Group on Inflammatory Bowel Disease. Asia Pacific Consensus Statements on Crohn’s disease. Part 1: Definition, diagnosis, and epidemiology: (Asia Pacific Crohn’s Disease Consensus—Part 1). J Gastroenterol Hepatol 2016 Jan;31:45–55.
Suzuki Y, Nakajima A, Kawato T, Iwata K, Motoyoshi M, Shuler CF. Identification of Smad-dependent and -independent signaling with transforming growth factor-beta type 1/2 receptor inhibition in palatogenesis. J Oral Biol Craniofac Res 2020;2:43–48.
Hu J, Chen Y, Huang Y, Su Y. Human umbilical cord mesenchymal stem cell-derived exosomes suppress dermal fibroblasts-myofibroblats transition via inhibiting the TGF-beta1/Smad 2/3 signaling pathway. Exp Mol Pathol 2020;115:104468.
Ballester B, Milara J, Montero P, Cortijo J. MUC16 is overexpressed in idiopathic pulmonary fibrosis and induces fibrotic responses mediated by transforming growth factor-beta1 canonical pathway. Int J Mol Sci 2021;12:6502.
Chen L, Yang T, Lu DW, Zhao H, Feng YL, Chen H, et al. Central role of dysregulation of TGF-beta/Smad in CKD progression and potential targets of its treatment. Biomed Pharmacother 2018;101:670–681.
Aragon E, Wang Q, Zou Y, Morgani SM, Ruiz L, Kaczmarska Z, et al. Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-beta signaling. Genes Dev 2019;33:1506–1524.
Gholami MD, Falak R, Heidari S, Khoshmirsafa M, Kazemi MH, Zarnani AH, et al. A truncated Snail1 transcription factor alters the expression of essential EMT markers and suppresses tumor cell migration in a human lung cancer cell line. Recent Pat Anticancer Drug Discov 2019;2:158–169.
Lee YJ, Park JH, Oh SM. Activation of NF-kappa B by TOPK upregulates Snail/Slug expression in TGF-beta1 signaling to induce epithelialmesenchymal transition and invasion of breast cancer cells. Biochem Biophys Res Commun 2020;1:122–129.
Aban CE, Lombardi A, Neiman G, Biani MC, La Greca A, Waisman A, et al. Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT. Sci Rep 2021;1:2048.
Bascetin R, Blay L, Kellouche S, Carreiras F, Picot CR, Briand M, et al. Fibronectin amyloid-like aggregation alters its extracellular matrix incorporation and promotes a single and sparsed cell migration. Exp Cell Res 2018;1:104–121.
Garrison CM, Schwarzbauer JE. Fibronectin fibril alignment is established upon initiation of extracellular matrix assembly. Mol Biol Cell 2021;8:739–752.
Fan Y, Kim DH, Gwak YS, Ahn D, Ryu Y, Chang S, et al. The role of substance P in acupuncture signal transduction and effects. Brain Behav Immun 2021;91:683–694.
Duan D, Tu Y, Yang X, Liu P. Electroacupuncture restores 5-HT system deficit in chronic mild stress-induced depressed rats. Evid Based Complement Alternat Med 2016;2016:7950635.
Li Y, Wu F, Cheng K, Shen XY, Lao LX. Mechanisms of Acupuncture for Inflammatory Pain. Acupunct Res 2018;8:467–475.
Pang P, Shi Y, Xu H, Deng L, Wu S, Chen X. Acupuncture methods put to the test for a tinnitus study: a Bayesian analysis. Complement Ther Med 2019;42:205–213.
Song XJ, Wang SY, Li YL, Zhang D. Analysis of the spectral characteristics of pure moxa stick burning by hyperspectral imaging and fourier transform infrared spectroscopy. Evid Based Complement Alternat Med 2016:1057878.
Li Y, Sun C, Kuang J, Ji C, Feng S, Wu J, et al. An in vitro and numerical study of moxibustion therapy on biological tissue. IEEE Trans Biomed Eng 2018;4:779–788.
Wang GY, Wang LL, Xu B, Zhang JB, Jiang JF. Effects of moxibustion temperature on blood cholesterol level in a mice model of acute hyperlipidemia: role of TRPV1. Evid Based Complement Alternat Med 2013:871704.
Matsuura K, Seta H, Haraguchi Y, Alsayegh K, Sekine H, Shimizu T, et al. TRPV-1-mediated elimination of residual iPS cells in bioengineered cardiac cell sheet tissues. Sci Rep 2016;6:21747.
Gouin O, L’Herondelle K, Lebonvallet N, Le Gall-Ianotto C, Sakka M, Buhe V, et al. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell 2017;9:644–661.
Cui M, Gosu V, Basith S, Hong S, Choi S. Polymodal transient receptor potential vanilloid type 1 nocisensor: structure, modulators, and therapeutic applications. Adv Protein Chem Struct Biol 2016;104:81–125.
Zhou X, **ong J, Lian Z. Predication of skin temperature and thermal comfort under two-way transient environments. J Therm Biol 2017;Pt A:15–20.
Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, et al. Pivotal role of cardiomyocyte TGF-beta signaling in the murine pathological response to sustained pressure overload. J Clin Invest 2011;6:2301–2312.
Lowe C, Aiken A, Day AG, Depew W, Vanner SJ. Sham acupuncture is as efficacious as true acupuncture for the treatment of IBS: a randomized placebo controlled trial. Neurogastroenterol Motil 2017;7:https://doi.org/10.1111/nmo.13040.
Author information
Authors and Affiliations
Contributions
Shi Y designed the study, Zhou J, Zhao JM, Wu P and Gao YL contributed to the patient enrollment, Bao CH and Weng ZJ performed the moxibustion and acupuncture procedure, Guo S and Zhou J performed the assays, Guo S and Zhang L analyzed the data, Guo S wrote the manuscript, Shi Y conducted the study and revised the manuscript collected data. All authors read and approved the final version of the manuscript submitted for publication.
Corresponding author
Additional information
Conflict of Interest
The authors declare that they have no competing interests.
Supported by the National Natural Science Foundation of China (Nos. 81674069 and 81473757)
Electronic Supplementary Material
Rights and permissions
About this article
Cite this article
Guo, S., Zhou, J., Zhang, L. et al. Acupuncture and Moxibustion Inhibited Intestinal Epithelial-Mesenchymal Transition in Patients with Crohn’s Disease Induced by TGF- β 1/Smad3/Snail Pathway: A Clinical Trial Study. Chin. J. Integr. Med. 28, 823–832 (2022). https://doi.org/10.1007/s11655-022-2888-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-022-2888-1