The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

Osama A Mohammed; Ahmed S Doghish; Mohannad Mohammad S Alamri; Muffarah Hamid Alharthi; Jaber Alfaifi; Masoud I E Adam; Abdullah Hassan Alhalafi; AbdulElah Al Jarallah AlQahtani; Assad Ali Rezigalla; Magaji Garba Taura; Adamu Imam Isa; Ahad Fuad Binafif; Mohammed A Attia; Elsayed A Elmorsy; Ayman A Yousef; Mustafa Ahmed Abdel-Reheim; Mohamed A Elkady

doi:10.1016/j.heliyon.2024.e27694

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

Heliyon. 2024 Mar 12;10(6):e27694. doi: 10.1016/j.heliyon.2024.e27694. eCollection 2024 Mar 30.

Authors

Osama A Mohammed¹, Ahmed S Doghish^{2

3}, Mohannad Mohammad S Alamri⁴, Muffarah Hamid Alharthi⁴, Jaber Alfaifi⁵, Masoud I E Adam⁶, Abdullah Hassan Alhalafi⁴, AbdulElah Al Jarallah AlQahtani⁷, Assad Ali Rezigalla⁸, Magaji Garba Taura⁸, Adamu Imam Isa⁹, Ahad Fuad Binafif¹⁰, Mohammed A Attia^{11

12}, Elsayed A Elmorsy^{11

13}, Ayman A Yousef¹⁴, Mustafa Ahmed Abdel-Reheim^{15

16}, Mohamed A Elkady³

Affiliations

¹ Department of Pharmacology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
² Department of Biochemistry, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
³ Department of Biochemistry and Molecular Biology, Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
⁴ Department of Family and Community Medicine, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
⁵ Department of Child Health, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
⁶ Department of Medical Education and Internal Medicine, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
⁷ Department of Internal Medicine, Division of Dermatology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
⁸ Department of Anatomy, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
⁹ Department of Physiology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia.
¹⁰ Blood Transfusion Services Center, Health Support Services Center, Ministry of Health, Riyadh, 11176, Saudi Arabia.
¹¹ Department of Clinical Pharmacology, Mansoura University, Mansoura, 35516, Egypt.
¹² Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, 11597, Saudi Arabia.
¹³ Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraydah, 51452, Saudi Arabia.
¹⁴ Chest Department, Benha University Hospitals, Qaliubyia, Egypt.
¹⁵ Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia.
¹⁶ Department of Pharmacology and Toxicology, Beni-Suef University, Beni.Suef, 62521, Egypt.

Abstract

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma.

Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs.

Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Keywords: Asthma; Diagnosis; IL-6; Matrix metalloproteinase-2; Pathophysiology; miR-196a2.