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Modulation of extracellular matrix using adenovirus vectors
1Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. richards@mcmaster.ca
Biochemical Society Transactions
|May 25, 2002
Summary
Oncostatin M (OSM) drives inflammation and extracellular matrix (ECM) deposition in the lungs. This study shows OSM
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular matrix (ECM) metabolism is dysregulated in inflammatory joint diseases like rheumatoid arthritis and lung fibrosis.
- Cytokines play key roles in ECM regulation; transforming growth factor-beta (TGF-β) is known to induce fibrosis, but the roles of other cytokines, like Oncostatin M (OSM), are less understood.
- OSM, part of the interleukin-6/leukaemia inhibitory factor (gp130) cytokine family, has demonstrated in vitro activities in regulating ECM components, including matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1).
Purpose of the Study:
- To investigate the in vivo effects of Oncostatin M (OSM) on extracellular matrix (ECM) metabolism and inflammatory responses in the lung.
- To compare the effects of OSM with those of transforming growth factor-beta (TGF-β) in a mouse model.
- To evaluate the utility of adenovirus-mediated gene delivery for studying ECM dynamics in vivo.
Main Methods:
- Adenovirus-mediated delivery of mouse OSM (AdmOSM) via intra-nasal administration into Balb/C mice.
- Induction of high OSM expression in the lung.
- Analysis of inflammatory cell infiltration (neutrophils, mononuclear cells) and collagen deposition at various time points post-administration.
Main Results:
- Intra-nasal administration of AdmOSM induced a significant inflammatory response by day 7.
- This response was characterized by elevated neutrophil and mononuclear cell counts in the lung.
- A marked increase in collagen deposition was observed, indicating significant ECM remodeling.
Conclusions:
- Oncostatin M (OSM) plays a role in modulating steady-state extracellular matrix (ECM) deposition in the lung.
- OSM can induce a vigorous inflammatory response, characterized by cell infiltration and increased collagen deposition.
- Adenovirus-mediated gene delivery systems are effective tools for studying ECM metabolism and inflammatory processes in vivo.