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.