Ukr.Biochem.J. 2024; Volume 96, Issue 6, Nov-Dec, pp. 66-73

doi: https://doi.org/10.15407/ubj96.06.066

HIF-2α level in adolescents with chronic inflammatory pathology of the upper gastrointestinal tract

04.12.2024   Uncategorized   No comments

N. S. Shevchenko1,2, N. V. Krutenko1*, L. L. Sukhova2,
O. M. Tsiura1, H. O. Shlieienkova1, K. V. Voloshyn1

1V. N. Karazin Kharkiv National University, Kharkiv, Ukraine;
2State Institution “Institute for Children and Adolescents Health Care
at the National Academy of Medical Sciences of Ukraine”, Kharkiv, Ukraine;
*e-mail: n.v.krutenko@karazin.ua

Received: 08 September 2024; Revised: 08 November 2024;
Accepted: 21 November 2024; Available on-line: 17 December 2024

Сhronic inflammatory diseases of the gastrointestinal tract are among the most common pathological conditions in adolescents. A significant role in the pathogenesis of gastrointestinal tract diseases is given to the functioning of the oxygen sensor system, the main mediator of which is hypoxia-inducible factor 2 (HIF-2α). Therefore, the purpose of the study was to determine the level of HIF-2α in the plasma of patients with chronic inflammatory pathology of the gastrointestinal tract, taking into account the endoscopic picture of the lesion, localization of the pathological process, age and gender of the patient. The study involved 70 adolescents aged 8-18 years with chronic gastroduodenitis (CGD), gastroesophageal reflux disease (GERD), gastric or duodenal ulcer and 25 peers who had been classified as healthy. The plasma concentration of HIF-2α was measured by a sandwich-linked ELISA. Helicobacter pylori infection was determined by urease test or by ELISA. According to the data obtained, the HIF-2α plasma level was higher in patients with chronic inflammatory gastrointestinal disease compared to the control group. In boys with chronic gastroduodenal disease, the level of HIF-2α was higher than in girls. CGD and GERD were characterized by a higher HIF-2α level in plasma than gastric and duodenal ulcers. The HIF-2α level did not depend on the age of the patients or the presence of Helicobacter pylori infection.

Keywords: , , , ,

References:

  1. Shlieienkova HO, Shevchenko NS, Tsiura OM, Krutenko NV, Voloshyn KV, Kovalivska SO. Analysis of the structure of comorbidity in children with gastrointestinal tract pathologies. Modern Gastroenterol. 2023;(6(134)):21-26. CrossRef
  2. Voloshyn K, Kovalivska S, Krutenko N, Tsiura O, Shlieienkova H. Analysis of the structure of pathology of the gastrointestinal tract in children. Actual Probl Mod Med. 2021;(8):22-31. (In Ukrainian). CrossRef
  3. Sorokman T, Gingulyak M. The effect of endogenous cortisol on the course of H. pylori-associated gastroduodenal diseases in adolescents. Child’s Health. 2022;17(5):244-248. CrossRef
  4. Mladenova I. Clinical relevance of Helicobacter pylori infection. J Clin Med. 2021;10(16):3473. PubMed, PubMedCentral, CrossRef
  5. Islek A, Yilmaz A, Elpek GO, Erin N. Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators. World J Gastroenterol. 2016;22(37):8349-8360. PubMed, PubMedCentral, CrossRef
  6. Ansari S, Yamaoka Y. Helicobacter pylori virulence factors exploiting gastric colonization and its pathogenicity. Toxins (Basel). 2019;11(11):677. PubMed, PubMedCentral, CrossRef
  7. Huo X, Agoston AT, Dunbar KB, Cipher DJ, Zhang X, Yu C, Cheng E, Zhang Q, Pham TH, Tambar UK, Bruick RK, Wang DH, Odze RD, Spechler SJ, Souza RF. Hypoxia-inducible factor-2α plays a role in mediating oesophagitis in GORD. Gut. 2017;66(9):1542-1554. PubMed, PubMedCentral, CrossRef
  8. Souza RF, Bayeh L, Spechler SJ, Tambar UK, Bruick RK. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol. 2017;37:93-99. PubMed, PubMedCentral, CrossRef
  9. Shevchenko NS, Krutenko NV, Zimnytska TV, Voloshyn KV. The role of hypoxia-inducible factors in the development of chronic pathology. Ukr Biochem J. 2021;93(4):18-25. CrossRef
  10. Zhang Q, Dunbar KB, Odze RD, Agoston AT, Wang X, Su T, Nguyen AD, Zhang X, Spechler SJ, Souza RF. Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett’s oesophagus patients. Gut. 2024;73(8):1269-1279. PubMed, PubMedCentral, CrossRef
  11. Souza RF. Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia. J Gastroenterol. 2017;52(7):767-776. PubMed, PubMedCentral, CrossRef
  12. Malkov MI, Lee CT, Taylor CT. Regulation of the hypoxia-inducible factor (HIF) by pro-inflammatory cytokines. Cells. 2021;10(9):2340. PubMed, PubMedCentral, CrossRef
  13. Ustaoglu A, Nguyen A, Spechler S, Sifrim D, Souza R, Woodland P. Mucosal pathogenesis in gastro-esophageal reflux disease. Neurogastroenterol Motil. 2020;32(12):e14022. PubMed, CrossRef
  14. Davis L, Recktenwald M, Hutt E, Fuller S, Briggs M, Goel A, Daringer N. Targeting HIF-2α in the tumor microenvironment: redefining the role of HIF-2α for solid cancer therapy. Cancers (Basel). 2022;14(5):1259. PubMed, PubMedCentral, CrossRef
  15. Solanki S, Devenport SN, Ramakrishnan SK, Shah YM. Temporal induction of intestinal epithelial hypoxia-inducible factor-2α is sufficient to drive colitis. Am J Physiol Gastrointest Liver Physiol. 2019;317(2):G98-G107. PubMed, PubMedCentral, CrossRef
  16. Shaqran TM, Ismaeel MM, Alnuaman AA, Al Ahmad FA, Albalawi GA, Almubarak JN, AlHarbi RS, Alaqidi RS, AlAli YA, Alfawaz KS, Daghriri AA. Epidemiology, causes, and management of gastro-esophageal reflux disease: a systematic review. Cureus. 2023;15(10):e47420. PubMed, PubMedCentral, CrossRef
  17. Xie X, Ren K, Zhou Z, Dang C, Zhang H. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol. 2022;22(1):58. PubMed, PubMedCentral, CrossRef
  18. Nirwan JS, Hasan SS, Babar ZU, Conway BR, Ghori MU. Global prevalence and risk factors of gastro-oesophageal reflux disease (GORD): systematic review with meta-analysis. Sci Rep. 2020;10(1):5814. PubMed, PubMedCentral, CrossRef
  19. Hashimoto H, Akimoto M, Maeda A, Shigemoto M, Yamashito K. Relation of hypoxia-inducible factor-1alpha to vascular endothelial growth factor and vasoactive factors during healing of gastric ulcers. J Cardiovasc Pharmacol. 2004;44(Suppl 1):S407-S409. PubMed, CrossRef
  20. Steinberger KJ, Eubank TD. The underexplored landscape of hypoxia-inducible factor 2 alpha and potential roles in tumor macrophages: a review. Oxygen (Basel). 2023;3(1):45-76. PubMed, PubMedCentral, CrossRef
  21. Amieva M, Peek RM Jr. Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology. 2016;150(1):64-78. PubMed, PubMedCentral, CrossRef
  22. Matak P, Heinis M, Mathieu JR, Corriden R, Cuvellier S, Delga S, Mounier R, Rouquette A, Raymond J, Lamarque D, Emile JF, Nizet V, Touati E, Peyssonnaux C. Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis. J Immunol. 2015;194(7):3259-3266. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.