Mmp19-KO Mouse

Mmp19, a member of the matrix metalloproteinase (MMP) family, plays crucial roles in extracellular matrix remodeling, which is involved in various physiological and pathological processes. MMPs can degrade all components of the extracellular matrix and numerous non-matrix proteins, and Mmp19 may be involved in pathways related to cell proliferation, adhesion, and migration [3,4].

In idiopathic pulmonary fibrosis (IPF), Mmp19 expression was significantly increased in the lung endothelial cells of IPF patients and bleomycin-induced mice. MMP19 promoted endothelial-to-mesenchymal transition (E(nd)MT), the migration and permeability of human pulmonary microvascular endothelial cells (HPMECs), stimulated monocyte infiltration into the alveolus, and aggravated pulmonary fibrosis. This was achieved by interacting with ET1 to promote E(nd)MT and via the SDF1/CXCR4 axis to stimulate monocyte infiltration. Additionally, MMP19 variants were identified in familial or sporadic IPF, and the plasma levels of MMP19 were significantly higher in IPF patients than in healthy controls [1,2]. In the context of T-cell development and cutaneous immune responses, MMP19-deficient mice showed impaired T-cell-mediated immune reactions, including limited influx of inflammatory cells, low keratinocyte proliferation, and reduced activated CD8(+) T cells in draining lymph nodes. This was related to low amounts of proinflammatory cytokines and an altered maturation of thymocytes [4].

In conclusion, Mmp19 is important in extracellular matrix remodeling and has significant implications in diseases like IPF, where it contributes to fibrosis through promoting E(nd)MT and monocyte infiltration. The study of Mmp19-deficient mice has revealed its role in T-cell-mediated cutaneous immune responses and T-cell development. These findings from model-based research help in understanding the biological functions of Mmp19 and its potential as a therapeutic target in related disease areas.

References:

1. Zhao, Weiming, Wang, Lan, Yang, Juntang, Rosas, Ivan, Yu, Guoying. 2023. Endothelial cell-derived MMP19 promotes pulmonary fibrosis by inducing E(nd)MT and monocyte infiltration. In Cell communication and signaling : CCS, 21, 56. doi:10.1186/s12964-023-01040-4. https://pubmed.ncbi.nlm.nih.gov/36915092/

2. Fan, Yali, Zheng, Chunming, Ma, Ruimin, Yang, Shuqiao, Ye, Qiao. 2023. MMP19 Variants in Familial and Sporadic Idiopathic Pulmonary Fibrosis. In Lung, 201, 571-580. doi:10.1007/s00408-023-00652-4. https://pubmed.ncbi.nlm.nih.gov/37971547/

3. Craig, Vanessa J, Zhang, Li, Hagood, James S, Owen, Caroline A. . Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. In American journal of respiratory cell and molecular biology, 53, 585-600. doi:10.1165/rcmb.2015-0020TR. https://pubmed.ncbi.nlm.nih.gov/26121236/

4. Beck, Inken M, Rückert, René, Brandt, Katja, Mentlein, Rolf, Sedlacek, Radislav. 2008. MMP19 is essential for T cell development and T cell-mediated cutaneous immune responses. In PloS one, 3, e2343. doi:10.1371/journal.pone.0002343. https://pubmed.ncbi.nlm.nih.gov/18523579/