Matrix Metalloproteinase-10: A Novel Biomarker for Idiopathic Pulmonary Fibrosis

Akihiko Sokai; Tomohiro Handa; Kiminobu Tanizawa; Toru Oga; Kazuko Uno; Tatsuaki Tsuruyama; Takeshi Kubo; Kohei Ikezoe; Yoshinari Nakatsuka; Kazuya Tanimura; Shigeo Muro; Toyohiro Hirai; Sonoko Nagai; Kazuo Chin; Michiaki Mishima

Disclosures

Respiratory Research. 2015;16(120) 

In This Article

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic pulmonary disease with a median survival of 3 to 5 years.[1] The clinical course of IPF is variable and unpredictable.[1–3] Because survival prediction requires both a large population and a long follow-up period, surrogate endpoints, such as declines in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO), are often used as primary endpoints in clinical studies instead of survival.[4,5] Regarding serum biomarkers, none have been established as a widespread clinical marker for IPF.[6,7] However, previous studies have suggested that biomarkers, such as Krebs von den lungen-6,[8] surfactant protein-A (SP-A),[9] CC chemokine ligand 18,[10] and matrix metalloproteinase (MMP)-7,[11] may serve as prognostic biomarkers for IPF.

MMPs have also been evaluated as biomarkers for IPF. MMPs are a family of proteinases whose active sites contain zinc. MMPs play a major role in the degradation and remodeling of the extracellular matrix (ECM), which consists primarily of glycoproteins, including collagens, proteoglycans, and fibronectin. MMPs also regulate multiple functions, such as cell proliferation, adhesion, migration, differentiation, and apoptosis, and play a pivotal role in the pathogenesis of IPF.[12] It has been reported that MMP-1, -2, and -7 are elevated in the serum and that MMP-3, -8, and -9 are elevated in the bronchoalveolar lavage fluid (BALF) in patients with IPF.[2,13,14] MMP-7 is one of the most extensively investigated MMPs in IPF. MMP-1 and -7 may be diagnostic biomarkers that distinguish IPF from other chronic lung diseases such as chronic obstructive pulmonary disease and sarcoidosis.[15] Previous studies have also demonstrated that serum MMP-7 correlates with both FVC and DLCO and is associated with survival in patients with IPF,[11,15] suggesting that MMP-7 may be a useful biomarker. Recently, however, it has been reported that not only MMP-7 but also other MMPs may play a significant role in the pathogenesis of IPF.[13,16]

As is the case with other MMPs, MMP-10 also plays a significant role in the degradation and remodeling of the ECM during tissue repair and vascular remodeling,[17,18] which suggests that MMP-10 is also an IPF biomarker candidate. However, in previous studies that screened serum MMPs in IPF, MMP-10 was not included in the analyses.[11,15] Therefore, little is known regarding the role of MMP-10 in IPF. In the present study, serum MMPs, including MMP-10, were comprehensively measured in patients with IPF, and their relationships with disease severity, short-term deterioration of pulmonary function, and overall survival were investigated.

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