Skip to main content
Top
Published in: BMC Gastroenterology 1/2023

Open Access 01-12-2023 | Helicobacter Pylori | Research

The evaluation of the MMP-2/TIMP-1 ratio in peptic ulcer and its association with refractory helicobacter pylori infection

Authors: Mohammad Negaresh, Elham Safarzadeh, Nasrin Fouladi, Somaieh Matin, Sanaz Pourfarzi

Published in: BMC Gastroenterology | Issue 1/2023

Login to get access

Abstract

Background

Helicobacter pylori (H. pylori) is one of the leading causes of peptic ulcers, and its treatment is a worldwide challenge. Matrix metalloproteinases and their inhibitors influence the development and healing of peptic ulcers. This study aimed to evaluate the ratios of matrix metalloproteinase-2 (MMP-2) to tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with peptic ulcers that are sensitive or resistant to H. pylori treatment and compare them with healthy individuals.

Methods

In this study, 95 patients were included and divided into two groups sensitive (41 patients) and resistant to treatment (54 patients). The results were compared with a control group of 20 participants with normal endoscopy and H. pylori-negative. After obtaining written informed consent, five ml of venous blood was taken to determine their serum MMP-2 and TIMP-1 levels using an enzyme-linked immunosorbent assay.

Results

In patients with H. pylori-induced peptic ulcers, the MMP-2/TIMP-1 ratio was significantly higher than the healthy controls (P < 0.05). MMP-2 level was associated with patients’ response to treatment (P < 0.05). The MMP-2/TIMP-1 ratio was higher in patients with simultaneous gastric and duodenal ulcers (P < 0.05).

Conclusion

It seems that peptic ulcer disease caused by infection with H. pylori increases the MMP-2/TIMP-1 ratio in patients with peptic ulcers. However, it might not be a good predictor of refractory H. pylori-induced peptic ulcer disease.
Literature
2.
go back to reference Keikha M, Ali-Hassanzadeh M, Karbalaei M. Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis. BMC Gastroenterol. 2020;20(1):1–11.CrossRef Keikha M, Ali-Hassanzadeh M, Karbalaei M. Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis. BMC Gastroenterol. 2020;20(1):1–11.CrossRef
3.
go back to reference Masclee GM, Valkhoff VE, Coloma PM, de Ridder M, Romio S, Schuemie MJ, et al. Risk of upper gastrointestinal bleeding from different drug combinations. Gastroenterology. 2014;147(4):784-92.e9.CrossRefPubMed Masclee GM, Valkhoff VE, Coloma PM, de Ridder M, Romio S, Schuemie MJ, et al. Risk of upper gastrointestinal bleeding from different drug combinations. Gastroenterology. 2014;147(4):784-92.e9.CrossRefPubMed
4.
go back to reference Chey WD, Wong BC, Gastroenterology PPCotACo. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–25.CrossRefPubMed Chey WD, Wong BC, Gastroenterology PPCotACo. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–25.CrossRefPubMed
5.
go back to reference Dechant F-X, Dechant R, Kandulski A, Selgrad M, Weber F, Reischl U, et al. Accuracy of different rapid urease tests in comparison with histopathology in patients with endoscopic signs of gastritis. Digestion. 1964;101(2):184–90.CrossRef Dechant F-X, Dechant R, Kandulski A, Selgrad M, Weber F, Reischl U, et al. Accuracy of different rapid urease tests in comparison with histopathology in patients with endoscopic signs of gastritis. Digestion. 1964;101(2):184–90.CrossRef
6.
go back to reference Rostami-Nejad M, Villanacci V, Mashayakhi R, Molaei M, Bassotti G, Zojaji H, et al. Celiac disease and Hp infection association in Iran. Rev Esp Enferm Dig. 2009;101(12):850.CrossRefPubMed Rostami-Nejad M, Villanacci V, Mashayakhi R, Molaei M, Bassotti G, Zojaji H, et al. Celiac disease and Hp infection association in Iran. Rev Esp Enferm Dig. 2009;101(12):850.CrossRefPubMed
7.
go back to reference Bruce MG, Bruden D, Newbrough D, Hurlburt DA, Hennessy TW, Morris JM, et al. The relationship between previous antimicrobial use, antimicrobial resistance and treatment outcome among Alaskans treated for Helicobacter pylori infection. GastroHep. 2019;1(4):172–9. Bruce MG, Bruden D, Newbrough D, Hurlburt DA, Hennessy TW, Morris JM, et al. The relationship between previous antimicrobial use, antimicrobial resistance and treatment outcome among Alaskans treated for Helicobacter pylori infection. GastroHep. 2019;1(4):172–9.
8.
go back to reference Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Investig. 2002;110(5):625–32.CrossRefPubMedPubMedCentral Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Investig. 2002;110(5):625–32.CrossRefPubMedPubMedCentral
9.
go back to reference Kim K-H, Burkhart K, Chen P, Frevert CW, Randolph-Habecker J, Hackman RC, et al. Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol. 2005;33(3):271–9.CrossRefPubMedPubMedCentral Kim K-H, Burkhart K, Chen P, Frevert CW, Randolph-Habecker J, Hackman RC, et al. Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol. 2005;33(3):271–9.CrossRefPubMedPubMedCentral
10.
go back to reference Posselt G, Crabtree JE, Wessler S. Proteolysis in helicobacter pylori-induced gastric cancer. Toxins (Basel). 2017;9(4):134.CrossRefPubMed Posselt G, Crabtree JE, Wessler S. Proteolysis in helicobacter pylori-induced gastric cancer. Toxins (Basel). 2017;9(4):134.CrossRefPubMed
11.
go back to reference Bergin PJ, Anders E, Sicheng W, Erik J, Jennie A, Hans L, et al. Increased production of matrix metalloproteinases in Helicobacter pylori-associated human gastritis. Helicobacter. 2004;9(3):201–10.CrossRefPubMed Bergin PJ, Anders E, Sicheng W, Erik J, Jennie A, Hans L, et al. Increased production of matrix metalloproteinases in Helicobacter pylori-associated human gastritis. Helicobacter. 2004;9(3):201–10.CrossRefPubMed
12.
go back to reference Koyama S. Significance of cell-surface expression of matrix metalloproteinases and their inhibitors on gastric epithelium and infiltrating mucosal lymphocytes in progression of Helicobacter pylori-associated gastritis. Scand J Gastroenterol. 2004;39(11):1046–53.CrossRefPubMed Koyama S. Significance of cell-surface expression of matrix metalloproteinases and their inhibitors on gastric epithelium and infiltrating mucosal lymphocytes in progression of Helicobacter pylori-associated gastritis. Scand J Gastroenterol. 2004;39(11):1046–53.CrossRefPubMed
13.
go back to reference Sadeghiani M, Bagheri N, Shahi H, Reiisi S, Rahimian G, Rashidi R, et al. cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori. J Immunoassay Immunochem. 2017;38(6):595–607.CrossRefPubMed Sadeghiani M, Bagheri N, Shahi H, Reiisi S, Rahimian G, Rashidi R, et al. cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori. J Immunoassay Immunochem. 2017;38(6):595–607.CrossRefPubMed
14.
go back to reference Rautelin HI, Oksanen AM, Veijola LI, Sipponen PI, Tervahartiala TI, Sorsa TA, et al. Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis. Ann Med. 2009;41(3):208–15.CrossRefPubMed Rautelin HI, Oksanen AM, Veijola LI, Sipponen PI, Tervahartiala TI, Sorsa TA, et al. Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis. Ann Med. 2009;41(3):208–15.CrossRefPubMed
15.
16.
go back to reference Syggelos S, Giannopoulou E, Gouvousis P, Andonopoulos A, Aletras A, Panagiotopoulos E. In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses. Osteoarthritis Cartilage. 2007;15(5):531–42.CrossRefPubMed Syggelos S, Giannopoulou E, Gouvousis P, Andonopoulos A, Aletras A, Panagiotopoulos E. In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses. Osteoarthritis Cartilage. 2007;15(5):531–42.CrossRefPubMed
17.
go back to reference Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010;20(3):161–8.CrossRefPubMedPubMedCentral Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010;20(3):161–8.CrossRefPubMedPubMedCentral
18.
go back to reference Almuntashiri S, Alhumaid A, Zhu Y, Han Y, Dutta S, Khilji O, et al. TIMP-1 and its potential diagnostic and prognostic value in pulmonary diseases. Chin Med J Pulmonary Crit Care Med. 2023;1(2):67–76.CrossRef Almuntashiri S, Alhumaid A, Zhu Y, Han Y, Dutta S, Khilji O, et al. TIMP-1 and its potential diagnostic and prognostic value in pulmonary diseases. Chin Med J Pulmonary Crit Care Med. 2023;1(2):67–76.CrossRef
19.
go back to reference Taylor SL, Rogers GB, Chen AC, Burr LD, McGuckin MA, Serisier DJ. Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis. Ann Am Thorac Soc. 2015;12(5):701–7.CrossRefPubMed Taylor SL, Rogers GB, Chen AC, Burr LD, McGuckin MA, Serisier DJ. Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis. Ann Am Thorac Soc. 2015;12(5):701–7.CrossRefPubMed
20.
go back to reference Cheng H-C, Yang H-B, Chang W-L, Chen W-Y, Yeh Y-C, Sheu B-S. Expressions of MMPs and TIMP-1 in gastric ulcers may differentiate H. pylori-infected from NSAID-related ulcers. Sci World J. 2012;2012:539316.CrossRef Cheng H-C, Yang H-B, Chang W-L, Chen W-Y, Yeh Y-C, Sheu B-S. Expressions of MMPs and TIMP-1 in gastric ulcers may differentiate H. pylori-infected from NSAID-related ulcers. Sci World J. 2012;2012:539316.CrossRef
21.
go back to reference Li SL, Zhao JR, Ren XY, Xie JP, Ma QZ, Rong QH. Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence. World J Gastroenterol. 2013;19(28):4590–5.CrossRefPubMedPubMedCentral Li SL, Zhao JR, Ren XY, Xie JP, Ma QZ, Rong QH. Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence. World J Gastroenterol. 2013;19(28):4590–5.CrossRefPubMedPubMedCentral
22.
go back to reference Calabrò A, Grappone C, Pellegrini G, Evangelista S, Tramontana M, Schuppan D, et al. Spatial and temporal pattern of expression of interstitial collagenase, stromelysin/transin, gelatinase A, and TIMP-1 during experimental gastric ulcer healing. Digestion. 2004;70(2):127–38.CrossRefPubMed Calabrò A, Grappone C, Pellegrini G, Evangelista S, Tramontana M, Schuppan D, et al. Spatial and temporal pattern of expression of interstitial collagenase, stromelysin/transin, gelatinase A, and TIMP-1 during experimental gastric ulcer healing. Digestion. 2004;70(2):127–38.CrossRefPubMed
23.
go back to reference Ogihara A, Kikuchi S, Hasegawa A, Kurosawa M, Miki K, Kaneko E, et al. Relationship between Helicobacter pylori infection and smoking and drinking habits. J Gastroenterol Hepatol. 2000;15(3):271–6.CrossRefPubMed Ogihara A, Kikuchi S, Hasegawa A, Kurosawa M, Miki K, Kaneko E, et al. Relationship between Helicobacter pylori infection and smoking and drinking habits. J Gastroenterol Hepatol. 2000;15(3):271–6.CrossRefPubMed
24.
go back to reference Moayyedi P, Axon AT, Feltbower R, Duffett S, Crocombe W, Braunholtz D, et al. Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection. Int J Epidemiol. 2002;31(3):624–31.CrossRefPubMed Moayyedi P, Axon AT, Feltbower R, Duffett S, Crocombe W, Braunholtz D, et al. Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection. Int J Epidemiol. 2002;31(3):624–31.CrossRefPubMed
25.
go back to reference Bujanda L. The effects of alcohol consumption upon the gastrointestinal tract. Am J Gastroenterol. 2000;95(12):3374–82.CrossRefPubMed Bujanda L. The effects of alcohol consumption upon the gastrointestinal tract. Am J Gastroenterol. 2000;95(12):3374–82.CrossRefPubMed
26.
go back to reference Fiotti N, Tubaro F, Altamura N, Grassi G, Moretti M, Dapas B, et al. Alcohol reduces MMP-2 in humans and isolated smooth muscle cells. Alcohol. 2008;42(5):389–95.CrossRefPubMed Fiotti N, Tubaro F, Altamura N, Grassi G, Moretti M, Dapas B, et al. Alcohol reduces MMP-2 in humans and isolated smooth muscle cells. Alcohol. 2008;42(5):389–95.CrossRefPubMed
27.
go back to reference Yu J, Yang P, Qin X, Li C, Lv Y, Wang X. Impact of smoking on the eradication of Helicobacter pylori. Helicobacter. 2022;27(1):e12860.CrossRefPubMed Yu J, Yang P, Qin X, Li C, Lv Y, Wang X. Impact of smoking on the eradication of Helicobacter pylori. Helicobacter. 2022;27(1):e12860.CrossRefPubMed
28.
go back to reference Ma L, Chow JYC, Cho CH. Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach. Am J Physiol Gastrointestin Liver Physiol. 1999;276(1):G238–48.CrossRef Ma L, Chow JYC, Cho CH. Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach. Am J Physiol Gastrointestin Liver Physiol. 1999;276(1):G238–48.CrossRef
29.
go back to reference Ning W, Dong Y, Sun J, Li C, Matthay MA, Feghali-Bostwick CA, et al. Cigarette smoke stimulates matrix metalloproteinase-2 activity via EGR-1 in human lung fibroblasts. Am J Respir Cell Mol Biol. 2007;36(4):480–90.CrossRefPubMed Ning W, Dong Y, Sun J, Li C, Matthay MA, Feghali-Bostwick CA, et al. Cigarette smoke stimulates matrix metalloproteinase-2 activity via EGR-1 in human lung fibroblasts. Am J Respir Cell Mol Biol. 2007;36(4):480–90.CrossRefPubMed
30.
go back to reference Garrow D, Delegge MH. Risk factors for gastrointestinal ulcer disease in the US population. Dig Dis Sci. 2010;55:66–72.CrossRefPubMed Garrow D, Delegge MH. Risk factors for gastrointestinal ulcer disease in the US population. Dig Dis Sci. 2010;55:66–72.CrossRefPubMed
Metadata
Title
The evaluation of the MMP-2/TIMP-1 ratio in peptic ulcer and its association with refractory helicobacter pylori infection
Authors
Mohammad Negaresh
Elham Safarzadeh
Nasrin Fouladi
Somaieh Matin
Sanaz Pourfarzi
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-023-02923-z

Other articles of this Issue 1/2023

BMC Gastroenterology 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.