Cell Elongation Induces Laminin α2 Chain Expression in Mouse Embryonic Mesenchymal Cells

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) α2 chain not present in round mesenchymal cells. LM α2 expression is reversible and switched on and off by altering the cell's shape in culture. In comparison, the expression of LM β1 and γ1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM α2. Dy/dy mice express very low levels of LM α2 and exhibit congenital muscular dystrophy. Lung SM cells isolated from adult dy/dy mice spread defectively and synthesized less SM α-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 α2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.

Nanopattern-induced changes in morphology and motility of smooth muscle cells

“…The elongation of cells and nucleus have been correlated with changes in gene expression profile and cell differentiation in other studies [15,[42][43][44]. The nucleus is mechanically integrated with the physical entity of the cell.…”

“…Meanwhile, the mechano-sensitive Ca 2+ channel in the nuclear membrane would induce release of Ca 2+ from the perinuclear space [42], which in turn would regulate gene expression. Relan et al has shown that cell elongation induces expression of laminin α2 (LM2) chain in mouse embryonic mesenchymal smooth muscle precursor cells [44]. Similarly, various studies have shown that distortion of nucleus would result in changes of gene and protein expression [15,43].…”

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

“…The elongation of cytoskeleton and nucleus have been correlated with changes in gene expression profile and cell differentiation in other studies [20][21][22][23]. Forces are transferred to the nucleus through actin-intermediate filament system during changes in cell shape [24].…”

“…The mechanical tension can rearrange the centromere through deformation of the nucleus [20] and mechano-transduction can affect the cellular structure and phenotypes in MSCs [25]. Cell elongation can also induce protein expression in embryonic mesenchymal smooth muscle precursor cells [23]. Similarly, various studies have shown that cell elongation and distortion of nucleus would result in changes of gene and protein expression [20,22].…”

Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering

“…58 This was confirmed by the observation that only spreading MSCs induced the expression of laminin a2 chain, which played a key role in myogenesis. 59 In the present study, hUCMSCs had a healthy spreading and elongated morphology in hUCMSC-microbead-AM, while cells maintained as dots in hUCMSC-AM. This is consistent with previous studies showing that alginate constructs (with or without RGD modification) had only nm-scale pores and cell spreading was inhibited in alginate.…”