Discussion
Several reports have indicated that MMP3 may play an important role in the process of lung pathology, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Studies conducted on animal models have found that the lungs of MMP3 gene deficient mice can be protected by inflammatory stimulation.[4,10,11] However, a study by Yamashita[12] (2016) indicated that MMP3 deficiency helps maintain the function of pulmonary surfactant to some extent and thereby protects the lungs from injury caused by physiological changes. This suggests that MMP3 plays a regulatory role in lung injury and repair. MMP3 is mainly secreted by fibroblasts and endothelial cells where inflammatory cells and cytokines can stimulate MMP3 secretion. It has been found that the non-matrix substrates of MMP3 are pro-inflammatory cytokines such as IL-1 β and TNF- α. Furthermore, MMP3 also activates other matrix metalloproteinases, including pro-MMP-1,3,7,8,9 and 13. While, the proteolysis function of MMP3 removes adhesion sites between cells and the matrix, contributing to in intracellular migration, MMP3 also plays a vital role in intercellular communication by regulating the activity of cytokines and chemokines, thus affecting and reflecting the progress of disease to a certain extent.[5,13,14]
The current study compared the serum MMP3 concentrations of the novel coronavirus pneumonia infected group with those of the non-infected group. Our results indicated that MMP3 may be utilized to monitor the state of COVID-19 patients. Some studies have identified the main pathological characteristics of COVID-19 patients as pulmonary inflammation and lung injury, in addition to which many severe cases may also develop into SARS.[15,16] Current literature on COVID-19 highlights the role of inflammation and immune responses in COVID-19, which, together with cytokine storm and proinflammatory factors like IL-1 β and TNF-α, undoubtedly contribute to the severity of disease.[17,18] It is important to consider the biological response of organisms to the SARS-CoV-2 infection from the point of view of protease and immune defense.
Hoffmann et al., [19] found that novel coronavirus (SARS-CoV-2), enters host cells in a manner similar to that of SARS-CoV, relying on ACE2 and serine protease, TMPRSS2. This complex process via which the virus infects cells, involves a variety of proteases, and thus it is important to investigate antiviral intervention through correlative proteases. A recent study by Phillips(2017) explored the role of various proteases in coronavirus infection and reported that zinc metalloproteases, such as matrix metalloproteinase, may be potential contributors to coronavirus fusion.[20]Therefore, it may be inferred that MMP3 is potentially associated with SARS-CoV-2 infection of host cells, via processes such as cell fusion. However, a literature review did not reveal any data on the association between MMP3 and coronavirus infection. In conclusion, future studies may lead to further progress in determining the relationship between MMP-3 and SARS-CoV-2 infection.
This study has some limitations. First of all, due to a small number of patients, this paper cannot provide a comprehensive review of the correlation between MMP3 levels and disease severity. As COVID-19, which is caused by a novel coronavirus virus, is a previously unknown disease, timely and effective measures have prevented the disease from causing a local pandemic. Another potential problem is that, conditionally, the study did not take other diseases associated with COVID-19 patients into account. A further study with more focus on excluding the influence of other factors is therefore suggested. Additionally, the future study may also contain the experiments on animal or cell model to explore more details.
In conclusion, the objective of the current study was to determine whether MMP3 levels have a role to play in the treatment of COVID-19 patients. Detection of serum MMP3 levels may be useful in assessing disease severity, as indicated by the positive correlation found between novel coronavirus pneumonia infected patients and non-infected patients. Insights gained from this study may assist in the monitoring, diagnosis, and treatment of COVID-19. Thus, further studies regarding the role of MMP3 in the pathology of COVID-19 are deemed to be useful.