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A Novel Stretching Platform for Applications in Cell and Tissue Mechanobiology
Published on: June 3, 2014
Regulation of Cyr61 gene expression by mechanical stretch through multiple signaling pathways
I Tamura1, J Rosenbloom, E Macarak
1Department of Histology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
American Journal of Physiology. Cell Physiology
|October 16, 2001
Summary
Mechanical stretch significantly increases cysteine-rich protein 61 (Cyr61) mRNA and protein levels in bladder smooth muscle cells. Signaling pathways involving protein kinase C, phosphatidylinositol 3-kinase, and Rho kinase, along with actin dynamics, regulate this Cyr61 gene response.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cysteine-rich protein 61 (Cyr61) is a signaling molecule involved in cell migration, adhesion, and proliferation.
- Cyr61 is encoded by an immediate early gene typically induced by serum growth factors.
Purpose of the Study:
- To investigate the regulation of Cyr61 gene expression by mechanical stretch in bladder smooth muscle cells.
- To identify key signaling pathways involved in the stretch-induced Cyr61 response.
Main Methods:
- Cultured bladder smooth muscle cells were subjected to cyclic mechanical stretch.
- Cyr61 mRNA and protein levels were quantified.
- Pharmacological agents targeting protein kinase C, phosphatidylinositol 3-kinase, Rho kinase, and actin dynamics were used to probe signaling pathways.
Main Results:
- Cyclic mechanical stretch induced a transient, sharp increase in Cyr61 mRNA levels.
- Stretch also led to an increase in Cyr61 protein, localized to the cytoplasm and nucleus.
- Inhibition of protein kinase C, phosphatidylinositol 3-kinase, and Rho kinase pathways partially blocked stretch-induced Cyr61 expression.
- Cyr61 gene expression was sensitive to actin cytoskeleton dynamics.
Conclusions:
- Mechanical stretch is a regulator of Cyr61 gene expression in bladder smooth muscle cells.
- Signaling pathways including PKC, PI3K, Rho kinase, and actin dynamics are involved in mediating the cellular response to mechanical stretch.
- This study provides insights into the molecular mechanisms governing Cyr61 regulation by mechanical stimuli.
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