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Cell elongation induces laminin alpha2 chain expression in mouse embryonic mesenchymal cells: role in visceral myogenesis.

Relan NK, Yang Y, Beqaj S, Miner JH, Schuger L - J. Cell Biol. (1999)

Bottom Line: In comparison, the expression of LM beta1 and gamma1 remains unchanged.These deficiencies were completely corrected by exogenous LM-2.The intestine, however, showed compensatory hyperplasia, perhaps related to its higher contractile activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

ABSTRACT
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) alpha2 chain not present in round mesenchymal cells. LM alpha2 expression is reversible and switched on and off by altering the cell's shape in culture. In comparison, the expression of LM beta1 and gamma1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM alpha2. Dy/dy mice express very low levels of LM alpha2 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 alpha2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.

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Related in: MedlinePlus

LM α2 chain in round and elongated cells of the embryonic lung. Western blot using a polyclonal antibody to LM-1/LM-2. Lane 1 (lung R), day 10.5 lungs, containing only round cells. Lane 2 (lung E), airways and surrounding mesenchyme microdissected from day 12 lungs, containing mainly elongated cells. mes. (lane 3), peripheral mesenchyme isolated from E12 lungs, containing only round cells (R). Lane 4 (R1), round undifferentiated mesenchymal cells before culture. Lane 5 (R2), round mesenchymal cells plated at high density to prevent cell spreading. LM α2 chain is seen only in elongated cells (lane 2).
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Figure 3: LM α2 chain in round and elongated cells of the embryonic lung. Western blot using a polyclonal antibody to LM-1/LM-2. Lane 1 (lung R), day 10.5 lungs, containing only round cells. Lane 2 (lung E), airways and surrounding mesenchyme microdissected from day 12 lungs, containing mainly elongated cells. mes. (lane 3), peripheral mesenchyme isolated from E12 lungs, containing only round cells (R). Lane 4 (R1), round undifferentiated mesenchymal cells before culture. Lane 5 (R2), round mesenchymal cells plated at high density to prevent cell spreading. LM α2 chain is seen only in elongated cells (lane 2).

Mentions: In vivo undifferentiated (round) mesenchymal cells do not express LM α2 chain, but elongated cells do. Here we determined whether the observations made in tissue cultures were relevant to the lung in vivo. At day 10.5 of gestation all the cells in the lung are round in shape. At this stage, the embryonic lung synthesizes LM α1 but not LM α2 (Fig. 3, first lane). At day 12 of gestation, most of the proximal peribronchial mesenchymal cells become spread/elongated and the distal epithelial cells become spread/flat. The undifferentiated mesenchymal cells, however, are still round. Western blots of microdissected airways and surrounding mesenchyme showed that the elongated cells express both LM α1 and α2 chains (Fig. 3, second lane), whereas Western blots of microdissected undifferentiated mesenchyme showed absence of LM α2 chains in round cells (Fig. 3, third lane).


Cell elongation induces laminin alpha2 chain expression in mouse embryonic mesenchymal cells: role in visceral myogenesis.

Relan NK, Yang Y, Beqaj S, Miner JH, Schuger L - J. Cell Biol. (1999)

LM α2 chain in round and elongated cells of the embryonic lung. Western blot using a polyclonal antibody to LM-1/LM-2. Lane 1 (lung R), day 10.5 lungs, containing only round cells. Lane 2 (lung E), airways and surrounding mesenchyme microdissected from day 12 lungs, containing mainly elongated cells. mes. (lane 3), peripheral mesenchyme isolated from E12 lungs, containing only round cells (R). Lane 4 (R1), round undifferentiated mesenchymal cells before culture. Lane 5 (R2), round mesenchymal cells plated at high density to prevent cell spreading. LM α2 chain is seen only in elongated cells (lane 2).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2168094&req=5

Figure 3: LM α2 chain in round and elongated cells of the embryonic lung. Western blot using a polyclonal antibody to LM-1/LM-2. Lane 1 (lung R), day 10.5 lungs, containing only round cells. Lane 2 (lung E), airways and surrounding mesenchyme microdissected from day 12 lungs, containing mainly elongated cells. mes. (lane 3), peripheral mesenchyme isolated from E12 lungs, containing only round cells (R). Lane 4 (R1), round undifferentiated mesenchymal cells before culture. Lane 5 (R2), round mesenchymal cells plated at high density to prevent cell spreading. LM α2 chain is seen only in elongated cells (lane 2).
Mentions: In vivo undifferentiated (round) mesenchymal cells do not express LM α2 chain, but elongated cells do. Here we determined whether the observations made in tissue cultures were relevant to the lung in vivo. At day 10.5 of gestation all the cells in the lung are round in shape. At this stage, the embryonic lung synthesizes LM α1 but not LM α2 (Fig. 3, first lane). At day 12 of gestation, most of the proximal peribronchial mesenchymal cells become spread/elongated and the distal epithelial cells become spread/flat. The undifferentiated mesenchymal cells, however, are still round. Western blots of microdissected airways and surrounding mesenchyme showed that the elongated cells express both LM α1 and α2 chains (Fig. 3, second lane), whereas Western blots of microdissected undifferentiated mesenchyme showed absence of LM α2 chains in round cells (Fig. 3, third lane).

Bottom Line: In comparison, the expression of LM beta1 and gamma1 remains unchanged.These deficiencies were completely corrected by exogenous LM-2.The intestine, however, showed compensatory hyperplasia, perhaps related to its higher contractile activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

ABSTRACT
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) alpha2 chain not present in round mesenchymal cells. LM alpha2 expression is reversible and switched on and off by altering the cell's shape in culture. In comparison, the expression of LM beta1 and gamma1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM alpha2. Dy/dy mice express very low levels of LM alpha2 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 alpha2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.

Show MeSH
Related in: MedlinePlus