Endogenous polypeptide growth factors in children with duodenal ulcer

Authors

DOI:

https://doi.org/10.15574/SP.2022.122.27

Keywords:

children, duodenal ulcer, epidermal growth factor (EGF), transforming growth factor α (TGF-α)

Abstract

Currently, the attention of many researchers is drawn to determine the features of the regeneration of the mucous membrane of the gastrointestinal tract in ulcers, as one of the most important protective factors in this pathology.

Purpose - to investigate the indicators of endogenous polypeptides (epidermal growth factor - EGF and transforming growth factor α-TGF-α) in the serum of children with duodenal ulcers.

Materials and methods. The study included 56 children aged 7-18 years (36 children with duodenal ulcer - the main group and 20 healthy children (comparison group). The content of endogenous polypeptides in serum was determined by enzyme-linked immunosorbent assay (ELISA) using the Human EGF ELISA Kit (Invitrogen, USA) for EGF and R&D system (USA) for TGF-α according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using parametric and non-parametric methods of evaluation of the obtained results.

Results. Slightly higher levels of EGF and TGF-α were found in boys of both subgroups of the main group (EGF: 561.45 [391.81-699.34] pg/ml and 544.67 [411.23-569.77] pg/ml, p>0.05; TGF-α: 47.91 [21.41-29.69] and 42.56 [35.45-49.21] pg/ml, p>0.05). Concentrations of endogenous factors in exacerbation of ulcerative process are higher than in remission (p<0.001) and in remission does not reach that in healthy children, p<0.01). In patients with severe duodenal ulcers, EGF and TGF-α concentrations are higher (p<0.01), which may be due to the maximum degree of inflammatory-destructive process.

Conclusions. The course of duodenal ulcer leads to disorders in the regulation of proliferative processes in the mucous membrane, which is manifested by increased levels of EGF and TGF-α in the serum of sick children, the more severe the course, the higher process.

The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interest was declared by the authors.

References

Aihara E, Matthis AL, Karns RA et al. (2016). Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type Alterations. Cell Mol Gastroenterol Hepatol. 2 (5): 625-647. https://doi.org/10.1016/j.jcmgh.2016.05.005; PMid:27766298 PMCid:PMC5042868

Amiri M, Seidler UE, Nikolovska K. (2021). The Role of pHi in Intestinal Epithelial Proliferation-Transport Mechanisms, Regulatory Pathways, and Consequences. Front Cell Dev Biol. 9: 618135. https://doi.org/10.3389/fcell.2021.618135; PMid:33553180 PMCid:PMC7862550

Baj J, Forma A, Sitarz M et al. (2020). Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells. 10 (1): 27. https://doi.org/10.3390/cells10010027; PMid:33375694 PMCid:PMC7824444

Belousova OYu, Kirianchuk NV, Pavlenko NV, Sysun LA. (2019). Echosonographic investigation of stomach in children with combined gas troesophageal reflux disease and chronic gastroduodenal pathology. Modern pediatrics. Ukraine. 4 (100): 3842. https://doi.org/10.15574/SP.2019.100.38

Berlanga-Acosta J, Gavilondo-Cowley J, López-Saura P et al. (2009). Epidermal growth factor in clinical practice - a review of its biological actions, clinical indications and safety implications. Int Wound J. 6 (5): 331-346. https://doi.org/10.1111/j.1742-481X.2009.00622.x; PMid:19912390 PMCid:PMC7951530

Beswick EJ, Pinchuk IV, Earley RB, Schmitt DA, Reyes VE. (2011). Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4+ T cell proliferation and development of regulatory T cells during Helicobacter pylori infection. Infect Immun. 79 (7): 2737-2745. https://doi.org/10.1128/IAI.01146-10; PMid:21482686 PMCid:PMC3191950

Blosse A, Lehours P, Wilson KT, Gobert AP. (2018). Helicobacter: Inflammation, immunology, and vaccines. Helicobacter. 23 (1): e12517. https://doi.org/10.1111/hel.12517; PMid:30277626 PMCid:PMC6310010

Burkitt MD, Duckworth CA, Williams JM, Pritchard DM. (2017). Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models. Dis Model Mech. 10 (2): 89-104. https://doi.org/10.1242/dmm.027649; PMid:28151409 PMCid:PMC5312008

Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C et al. (2020). The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 21 (24): 9739. Published 2020 Dec 20. https://doi.org/10.3390/ijms21249739; PMid:33419373 PMCid:PMC7767220

Gopcevic KR, Gkaliagkousi E, Nemcsik J et al. (2021). Pathophysiology of Circulating Biomarkers and Relationship With Vascular Aging: A Review of the Literature From VascAgeNet Group on Circulating Biomarkers, European Cooperation in Science and Technology Action 18216. Front Physiol. 12: 789690. https://doi.org/10.3389/fphys.2021.789690; PMid:34970157 PMCid:PMC8712891

Gunawardhana N, Jang S, Choi YH et al. (2018). Helicobacter pylori-Induced HB-EGF Upregulates Gastrin Expression via the EGF Receptor, C-Raf, Mek1, and Erk2 in the MAPK Pathway. Front Cell Infect Microbiol. 7: 541. https://doi.org/10.3389/fcimb.2017.00541; PMid:29379775 PMCid:PMC5775237

Kolesov SA. (2010). Concentration of epidermal growth factor in biosubstrates and the number of macrophages during defect healing in children and adolescents with duodenal ulcer. Klinicheskaya laboratornaya diagnostika. 1: 11-12.

Kosone T, Takagi H, Kakizaki S et al. (2006). Integrative roles of transforming growth factor-alpha in the cytoprotection mechanisms of gastric mucosal injury. BMC Gastroenterol. 6: 22. Published 2006 Aug 1. https://doi.org/10.1186/1471-230X-6-22; PMid:16879752 PMCid:PMC1552080

Leite M, Marques MS, Melo J et al. (2020). Helicobacter Pylori Targets the EPHA2 Receptor Tyrosine Kinase in Gastric Cells Modulating Key Cellular Functions. Cells. 9 (2): 513. https://doi.org/10.3390/cells9020513; PMid:32102381 PMCid:PMC7072728

Lu SY, Guo S, Chai SB et al. (2021). Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target. Biomed Res Int: 2648065. https://doi.org/10.1155/2021/2648065; PMid:34195260 PMCid:PMC8214476

Masuda H, Tanaka R, Fujimura S et al. (2014). Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential. J Am Heart Assoc. 3 (3): e000743. https://doi.org/10.1161/JAHA.113.000743; PMid:24965023 PMCid:PMC4309104

Ministry of Health of Ukraine. (2013). Order of the Ministry of Health of Ukraine No. 59 of January 29, 2013. Unified clinical protocols of medical care for children with diseases of the digestive system. Normative document of the Ministry of Health of Ukraine.

Nguyen TT, Kim SJ, Park JM, Hahm KB, Lee HJ. (2015). Repressed TGF-β signaling through CagA-Smad3 interaction as pathogenic mechanisms of Helicobacter pylori-associated gastritis. J Clin Biochem Nutr. 57 (2): 113-120. https://doi.org/10.3164/jcbn.15-38; PMid:26388668 PMCid:PMC4566024

Owyang SY, Zhang M, El-Zaatari M et al. (2020). Dendritic cell-derived TGF-β mediates the induction of mucosal regulatory T-cell response to Helicobacter infection essential for maintenance of immune tolerance in mice. Helicobacter. 25 (6): e12763. https://doi.org/10.1111/hel.12763; PMid:33025641 PMCid:PMC7885176

Sorokman TV, Moldova PM, Makarova ОV. (2020). Prospects for the use of antimicrobial peptides as antihelicobacterial agents in pediatric practice. Modern Pediatrics. Ukraine. 8 (112): 47-54. https://doi.org/10.15574/SP.2020.112.47

Tarnawski AS, Ahluwalia A. (2021). The Critical Role of Growth Factors in Gastric Ulcer Healing: The Cellular and Molecular Mechanisms and Potential Clinical Implications. Cells. 10 (8): 1964. Published 2021 Aug 2. https://doi.org/10.3390/cells10081964; PMid:34440733 PMCid:PMC8392882

Thomas DM, Nasim MM, Gullick WJ, Alison MR. (1992). Immunoreactivity of transforming growth factor alpha in the normal adult gastrointestinal tract. Gut. 33 (5): 628-631. https://doi.org/10.1136/gut.33.5.628; PMid:1612477 PMCid:PMC1379291

Zeng F, Harris RC. (2014). Epidermal growth factor, from gene organization to bedside. Semin Cell Dev Biol. 28: 2-11. https://doi.org/10.1016/j.semcdb.2014.01.011; PMid:24513230 PMCid:PMC4037350

Zhang L, Yuan Y, Yeh LK et al. (2020). Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma. Invest Ophthalmol Vis Sci. 61 (8): 20. https://doi.org/10.1167/iovs.61.8.20; PMid:32668000 PMCid:PMC7425719

Zhukova YeA, Vidmanova TA, Viskova IN, Kolesov SA, Korkotashvili LV, Kankova NJu. (2013). Changes of Epidermal Growth Factor Level in Blood Serum, Saliva and Gastric Juice in Children with Duodenal Ulcer. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk. 12: 36-40.

https://doi.org/10.15690/vramn.v68i12.857

Published

2022-03-30

Issue

Section

Original articles