# MATRIX ADHESION OF AGING HUMAN DERMAL FIBROBLASTS

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1992 · $139,016

## Abstract

Aging processes in human skin reflect to some degree afteration of
the communication between cells of this complex tissue and their
extracellular matrices.  This project examines the mechanisms of
matrix adhesion of human papillary and reticular dermal
fibroblasts mediated by collagen and fibronectin(FN), as well as
afteration of these mechanisms upon in vitro aging.  Aging-related
afterations in these adhesion mechanisms have now been identified.
Both integrin and heparan sulfate proteoglycan binding activities
of FN are required for many cell responses; the two aging
processes generate shifts in cell dependence upon these two
"receptor" activities.  Cycloheximide pretreatment of cells has
also revealed deficiences of collagen-specific, but not
FN-specific, receptors for F-actin stress fiber reorganization in
aging cells; cells from Down's syndrome patients, a genetic model
of premature aging, share this aging-related deficiency in
adhesion responses.  Molecular biological analyses of FN pre-mRNA
splicing in these cells (using a novel double-primer extension
assay) have also identified changes in the splicing pattern in the
complex IIICS region of the FN transcript which harbors a unique
cell-binding domain and which is aging-related.

We will continue to test the hypothesis that matrix changes occur
in human dermis as a consequence of aging processes and that these
changes after dermal fibroblast responses at several levels of
regulation.  Three specific aims will be pursued in our analyses.
(a) We will identify the matrix adhesion receptors that become
deficient in aging dermal fibroblasts from several normal
individuals and from patients suffering from premature aging
(Down's, Werner's, and progeria).  The mechanisms of receptor
deficiency will be described in clonal and mixed populations. (b)
Transcriptional regulation of collagen- and FN-specific integrin
genes will be analyzed during aging, as well as their clonal
variabilfty within aging populations. (c) We will determine
whether receptor deficiency in aging cells down-regulates
expression of genes which are stringently dependent upon the
matrix to which cells are anchored.  These studies will provide
further insight into the two-way communication(s) that occurs in
the human dermis between papillary and reticular fibroblasts and
their surrounding matrices, regulation of these communication
processes, and their alteration upon aging in vivo or in vitro.

## Key facts

- **NIH application ID:** 3122172
- **Project number:** 1R01AG010213-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** LLOYD A CULP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $139,016
- **Award type:** 1
- **Project period:** 1992-08-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122172

## Citation

> US National Institutes of Health, RePORTER application 3122172, MATRIX ADHESION OF AGING HUMAN DERMAL FIBROBLASTS (1R01AG010213-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122172. Licensed CC0.

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