Cell elongation induces laminin alpha 2 chain expression in mouse embryonic mesenchymal cells: Role in visceral myogenesis

Bronchial smooth muscle (SM) mesenchymal cell precursors change their shape from round to spread/elongated while undergoing differentiation. Here we s how that this change in cell shape induces the expression of laminin (LM) a lpha 2 chain not present in round mesenchymal cells. LM alpha 2 expression is reversible and switched on and off by altering the cell's shape in cultu re. In comparison, the expression of LM beta 1 and gamma(1) remains unchang ed. Functional studies showed that mesenchymal cell spreading and further d ifferentiation into SM are inhibited by an antibody against LM alpha 2. Dy/ dy mice express very low levels of LM alpha 2 and exhibit congenital muscul ar dystrophy. Lung SM cells isolated from adult dy/dy mice spread defective ly and synthesized less SM alpha-actin, desmin, and SM-myosin than controls , These deficiencies were completely corrected by exogenous LM-2, On histol ogical examination, dy/dy mouse airways and gastrointestinal tract had shor ter SM cells. and lungs from dy/dy mice contained less SM-specific protein. The intestine, however, showed compensatory hyperplasia, perhaps related t o its higher contractile activity. This study therefore demonstrated a nove l role for the LM alpha 2 chain in SM myogenesis and showed that its decrea se in dy/dy mice results in abnormal SM.