Co-expression of matrix metalloproteinase-7 and cellular senescence markers in fibrosing interstitial lung diseases

<bold>RATIONALE:</bold> Cellular senescence is a crucial mechanism implicated in the pathogenesis of pulmonary fibrosis. The extracellular matrix and cell-to-matrix interactions may contribute to cellular senescence. While matrix metalloproteinase-7 (MMP-7) is emerging as a significant biomarker for idiopathic pulmonary fibrosis (IPF), its association with cellular senescence in other fibrosing interstitial lung diseases (f-ILDs) remains unknown. <bold>Objective:</bold> To assess the relation between MMP-7 and cellular senescence markers in patients with f-ILD, and their association with different histopathological patterns. <bold>Methods:</bold> Immunohistochemistry of senescence markers (p16, p21) and MMP-7 was performed on lung biopsies of f-ILD patients (13 IPF and 17 non-IPF f-ILD) at diagnosis and 14 controls, and quantified by semi-quantitative analysis. All patients were classified following international guidelines. Histopathological patterns were revised by expert pathologists. <bold>Results:</bold> We found that senescence markers (p16 and p21) were present in both groups, IPF and non-IPF f-ILD patients, but not in controls. These markers were primarily observed in epithelial cells, though not exclusively, and showed notable consistency with MMP-7 distribution, indicating co-expression of both senescence markers and MMP-7. Senescence markers and MMP-7 were predominantly found in usual interstitial pneumonia (UIP) pattern, regardless of the concurrent disease. <bold>CONCLUSION:</bold> There might be an association between MMP-7 and the accelerated aging and senescence process of f-ILD, potentially impacting lung remodelling, particularly, although not exclusively, in UIP pattern seen in both IPF and non-IPF f-ILD patients.