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© The Rockefeller University Press, 0021-9525/1999/12/1341/ $5.00
The Journal of Cell Biology, Volume 147, Number 6, December 13, 1999 1341-1350

Original Article

Cell Elongation Induces Laminin {alpha}2 Chain Expression in Mouse Embryonic Mesenchymal Cells: Role in Visceral Myogenesis

Nand K. Relana, Yan Yanga, Safedin Beqaja, Jeffrey H. Minerb, and Lucia Schugera
a Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201
b Department of Medicine, Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110

Correspondence to: Lucia Schuger, Department of Pathology, Wayne State University, 540 E. Canfield, Detroit, MI 48201. Tel:(313) 577-5651 Fax:(313) 577-0057 E-mail:lschuger{at}med.wayne.edu.

Bronchial smooth muscle (SM) mesenchymal cell precursors change their shape from round to spread/elongated while undergoing differentiation. Here we show that this change in cell shape induces the expression of laminin (LM) {alpha}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 culture. In comparison, the expression of LM ß1 and {gamma}1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation 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 muscular dystrophy. Lung SM cells isolated from adult dy/dy mice spread defectively and synthesized less SM {alpha}-actin, desmin, and SM-myosin than controls. These deficiencies were completely corrected by exogenous LM-2. On histological examination, dy/dy mouse airways and gastrointestinal tract had shorter SM cells, and lungs from dy/dy mice contained less SM-specific protein. The intestine, however, showed compensatory hyperplasia, perhaps related to its higher contractile activity. This study therefore demonstrated a novel role for the LM {alpha}2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.

Key Words: laminin, smooth muscle, myogenesis, dy/dy mice, lung


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