Restoration to a quiescent and contractile phenotype from a proliferative phenotype of myofibroblast-like human aortic smooth muscle cells by cultureon type IV collagen gels

Aortic smooth muscle cells (A-SMC) undergo phenotypic transition to a synth etic and proliferative state and become fibroblast-like cells upon serial p assage with culture on plastic dishes, especially in the presence of serum. Such fibroblast-like cells (M-SMC) derived from A-SMC may correspond to th e cells identified pathologically as myofibroblasts. We examined the effect s of type IV collagen gels used as a culture substrate on the morphology an d proliferation of M-SMC. The M-SB IC underwent extreme elongation in shape when cultured on rigid type IV collagen gels, and eventually formed cell-t o-cell junctions with the elongated processes. In contrast, M-SMC showed a spindle-like cell shape on dishes coated with a type IV collagen solution o r type I collagen solution, or on type I collagen gels or fragile type IV c ollagen gels, Cell proliferation was totally repressed by culture on rigid type IV collagen gels for over 10 days, while the highest proliferative act ivity was seen for cells grown on dishes coated with type IV collagen solut ion. The expression of smooth muscle myosin heavy chains, specific markers for contractile A-SMC, was acquired by M-SMC cultured on rigid type IV coll agen gels for 3 days, while M-SMC cultured on type IV collagen-coated dishe s continued to show no expression. These results suggest that the quiescent and contractile phenotype of A-SMC might be restored in M-SMC by culture o n rigid type IV collagen gels, even after they have become myofibroblastic.