title: Mmp1a and Mmp1b are not functional orthologs to human MMP1 in cigarette smoke induced lung disease.
abstract: Matrix Metalloproteinase 1 (MMP1, collagenase-1) expression is implicated in a number of diseased states including emphysema and malignant tumors. The cigarette-smoke induced expression of this interstitial collegenase has been studied extensively and its inhibition proposed as a novel therapeutic treatment for tobacco related diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. However, a limitation in MMP1 research is the inability to take advantage of natural in vivo studies as most research has been performed in vitro or via animal models expressing human forms of the gene due to the lack of a rodent ortholog of MMP1. The present study examines the function of two possible mouse orthologs of human MMP1 known as Mmp1a and Mmp1b. Using genomic sequence analysis and expression analysis of these enzymes, the data demonstrate that neither MMP1a nor MMP1b behave in the same manner as human MMP1 in the presence of cigarette smoke. These findings establish that the two commonly proposed orthologs of MMP1, Mmp1a and Mmp1b, provide substantial limitations for use in examining MMP1 induced lung disease in mouse models of cigarette smoke emphysema.
authors.affiliation: Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, P&S 12-402, New York, NY 10032 USA.
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Carver
authors.affiliation: Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, P&S 12-402, New York, NY 10032 USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Anguiano
authors.affiliation: Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, P&S 12-402, New York, NY 10032 USA.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: D'Armiento
authors.affiliation: Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, P&S 12-402, New York, NY 10032 USA. Electronic address: ts2425@cumc.columbia.edu.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomi
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D012906:Smoke / Q000009:adverse effects*; D013045:Species Specificity; D062789:Tobacco Products / Q000633:toxicity*
chemical_list: D012906:Smoke; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C425310:Mmp1a protein, mouse; C425311:Mmp1b protein, mouse
keywords: Animal model; Gene expression regulation; Mice; Proteinase