COMPARTMENTS OF GROWTH ARREST DURING CELLULAR AGING

Project: Research project

Project Details

Description

The aim of this proposed work is to test the hypothesis that prostaglandins
of the series (PGE1 and PGE2) induce a state of temporary or transient
growth arrest in human diploid fibroblasts (HDF) grown in vitro. The
initial mechanism whereby transient growth arrest in induced involves an
alteration in fibronectin (hybridoma HFN 7.1). Further, the relationship
between an alternation in fibronectin mediated cell adhesion by PGE. This
will be tested directly in experiments using a quantitative cellular
adhesion assay and in experiments using a monoclonal antibody directed
against human fibronectin mediated cell adhesion by PGE and proliferative
capacity will be tested in experiments that compare the fluorescence
pattern of fibronectin and the ability to progress to S phase in the same
cells. Alterations in the regulation of this growth arrested state during
aging will be examined by comparing the response of fibroblasts from donors
of 29, 59 and 92 years, as well as those from a patient with progeria, to
inducers (PGE1 and PGE2) and inhibitors (hydrocortisone) of transient
growth arrest. A second aim of this work is to develope quantitative
methods to study the roles of other defined medium components in modulating
growth arrest in HDF. These methods, multiparameter flow cytometry and
cell fusion assays, provide ways to discriminate between those factors that
modulate transient growth arrest and those that affect permanent growth
arrest. Since most fibroblasts in vivo are not in a state of either
continuous proliferation or in a state of terminal growth arrest, an
understanding of the mechanisms that govern transient growth arrest in
vitro could serve to generate new knowledge about the regulation of
fibroblasts in humans.
StatusFinished
Effective start/end date9/29/832/28/87

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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