Cell shape-dependent pathway of plasminogen activator inhibitor type-1 gene expression requires cytoskeletal reorganization

Journal of Cellular Physiology
K Hawks, P J Higgins

Abstract

Synthesis of plasminogen activator inhibitor type-1 (PAI-1), a major physiological modulator of plasmin generation, is regulated by growth factors and changes in cell shape. To evaluate the specific relationship between PAI-1 gene expression and cytoarchitecture, serum-free cultures of quiescent rat kidney (NRK) cells were exposed to cytochalasin D (CD) at concentrations that disrupt microfilament structure. Treatment with 1-10 microM CD resulted in an increased 1) incidence of rounded cells, 2) relative PAI-1 mRNA content, and 3) fraction of PAI-1 protein-expressing cells. Abrupt increases in each response were evident at a final concentration of 5 microM CD. Maximal levels of induced PAI-1 transcripts (18-fold that of control) occurred 4 hours post-CD addition and declined thereafter but remained elevated (by at least tenfold) for 24 hours. Assessment of the metabolic requirements for CD-induced PAI-1 expression by using the protein synthesis inhibitors puromycin and cycloheximide indicated that PAI-1 transcripts were regulated in a complex manner in response to CD. The predominant mode of induction reflected secondary (protein synthesis-dependent) metabolic processes, although a minor, albeit significant, primary (protein sy...Continue Reading

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Citations

Apr 22, 2003·Journal of Cellular Physiology·Rohan Samarakoon, Paul J Higgins
Sep 19, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lea M BeaulieuFrank C Church

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