Abstract
BackgroundCanine idiopathic pulmonary fibrosis (CIPF) is a chronic, interstitial lung disease that mainly affects West Highland white terriers (WHWTs) and is characterized by excessive deposition of extracellular matrix (ECM) in the lung. Matrix metalloproteinases (MMPs) participate in remodeling of ECM.ObjectivesTo compare metalloproteinase‐2, ‐7 and ‐9 activities in blood or bronchoalveolar lavage fluid (BALF) samples or both of CIPF WHWTs with healthy WHWTs, healthy dogs of other breeds, and dogs with other lung diseases and determine if these MMPs could be used as diagnostic and prognostic markers for CIPF.AnimalsForty‐four CIPF WHWTs, 24 dogs with chronic bronchitis (CB), 17 with eosinophilic bronchopneumopathy (EBP), 10 with bacterial pneumonia, 39 healthy WHWTs, and 35 healthy dogs of other breeds.MethodsCross‐sectional observational study. Pro‐MMP and active MMP activities were analyzed by zymography.ResultsIn serum, significantly higher (P < .01) pro‐MMP‐7 activities were observed in CIPF WHWTs compared to healthy dogs of other breeds, dogs with CB and dogs with EBP. In BALF of CIPF WHWTs, both pro‐MMP‐9 and pro‐MMP‐2 activities were significantly higher (P < .01) compared to healthy WHWTs, but these differences were not detected in plasma. The CIPF WHWTs had significantly higher (P < .05) activities of pro‐MMP‐9 compared to dogs with CB and of pro‐MMP‐2 compared to dogs with CB and EBP. No statistically significant prognostic factors were observed in CIPF WHWTs.Conclusions and clinical relevanceSerum MMP‐7 and BALF MMP‐2 and ‐9 potentially may be useful diagnostic markers but not prognostic markers for CIPF.
Highlights
Matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases
We compared the activities of MMP-7 in blood and MMP-2 and -9 in bronchoalveolar lavage fluid (BALF) of Canine idiopathic pulmonary fibrosis (CIPF) dogs, dogs with other lung diseases, and healthy dogs
Our findings suggest that especially serum MMP-7 and BALF MMP-2 and -9 may be potential diagnostic but not prognostic markers for CIPF
Summary
Matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases They are divided into subgroups based on substrate specificity and structure.[1] Twenty-three different MMPs have been identified in humans.[2] These endopeptidases degrade both extracellular matrix (ECM) proteins, such as collagen and fibronectin, and non-ECM proteins, such as cytokines and growth factors. Matrix metalloproteinases are secreted as inactive pro-forms that require activation to form a functional active enzyme.[1] In healthy tissue, MMP activity is low or absent, but it increases in pathological conditions, including lung diseases such as idiopathic pulmonary fibrosis (IPF) in humans[3] and in physiological repair and remodeling processes.[1]. We hypothesized that MMP activities would be increased in CIPF WHWTs and that, as in humans, especially blood MMP-7 would be a potential diagnostic and prognostic marker for CIPF
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