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• W2022740039 endingPage "L1066" @default.
• W2022740039 startingPage "L1059" @default.
• W2022740039 abstract "Increased airway smooth muscle (ASM) mass and infiltration by mast cells are key features of airway remodeling in asthma. We describe a model to investigate the relationship between ASM, the extracellular matrix, mast cells, and airway remodeling. ASM cells were cultured in a three-dimensional (3-D) collagen I gel (3-D culture) alone or with mast cells. Immunocytochemistry and Western blotting of ASM in 3-D cultures revealed a spindle-shaped morphology and significantly lower alpha-smooth muscle actin and vimentin expression than in ASM cultured in monolayers on collagen type I or plastic (2-D culture). In 3-D cultures, basal ASM proliferation, examined by Ki67 immunocytochemistry, was reduced to 33 +/- 7% (P < 0.05) of that in 2-D cultures. The presence of mast cells in cocultures increased ASM proliferation by 1.8-fold (P < 0.05). Gelatin zymography revealed more active matrix metalloproteinase (MMP)-2 in 3-D than in 2-D culture supernatants over 7 days. Functional MMP activity was examined by gel contraction. The spontaneous gel contraction over 7 days was significantly inhibited by the MMP inhibitor ilomastat. Mast cell coculture enhanced ASM gel contraction by 22 +/- 16% (not significant). Our model shows that ASM has different morphology, with lower contractile protein expression and basal proliferation in 3-D culture. Compared with standard techniques, ASM synthetic function, as shown by MMP production and activity, is sustained over longer periods. The presence of mast cells in the 3-D model enhanced ASM proliferation and MMP production. Airway remodeling in asthma may be more accurately modeled by our system than by standard culture systems." @default.
• W2022740039 created "2016-06-24" @default.
• W2022740039 creator A5017673380 @default.
• W2022740039 creator A5053196775 @default.
• W2022740039 creator A5071572427 @default.
• W2022740039 date "2009-06-01" @default.
• W2022740039 modified "2023-09-27" @default.
• W2022740039 title "Use of a three-dimensional cell culture model to study airway smooth muscle-mast cell interactions in airway remodeling" @default.
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• W2022740039 doi "https://doi.org/10.1152/ajplung.90445.2008" @default.
• W2022740039 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19346431" @default.
• W2022740039 hasPublicationYear "2009" @default.
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