# Surgical Wound Repair: fibroproliferative responses to cutaneous injury

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $299,338

## Abstract

Hypertrophic scars in deep dermal burns comprise a devastating physical disfigurement for which there is no
reliable treatment or prevention. Patients suffer from chronic discomfort due to raised, red, contracted scars.
Chronic neuropathic pain constitutes one common complaint; itching impedes ability to sleep and work and
negatively impacts quality of life. The Duroc porcine fibroproliferative model offers an opportunity for pre-
clinical testing of therapeutic interventions, but is expensive and involves multiple surgeries on large vertebrate
animals. Observations that cultured Duroc and Yorkshire fibroblasts maintain a fibroproliferative genotype and
phenotype suggest a potential for mechanistic hypothesis development without involving large numbers of
pigs. A barrier to understanding hypertrophic scar pathophysiology has been limited ability to define
fibroproliferative signaling. Our plan to use RNA sequencing (RNA-Seq) to assess Duroc and Yorkshire
fibroblast genomic responses will identify unprecedented expression patterns. Our repository of human DNA
with a prospectively collected clinical database allows us to correlate genetic results with severity of scarring.
This proposal marries cutting edge methodologies with unique repositories to determine cellular events leading
to impaired healing and to identify therapeutic interventions for wound repair. Our novel hypothesis is that
Duroc porcine fibroproliferation represents a reproducible biological model of human cutaneous hypertrophic
scar formation. We propose 3 specific aims: Aim 1: To define the differential transcriptome expression induced
by the fibroproliferative mediator transforming growth factor β1 (TGFβ1) in Duroc and Yorkshire fibroblasts.
Our hypothesis for Aim 1 is that cultured Duroc fibroblasts have an intrinsic TGFβ1-resistent fibroproliferative
genotype that represents a reproducible in vitro model that can be used to study cutaneous scarring. We will
use RNA Seq to identify novel differentially expressed genes in Yorkshire and Duroc fibroblasts and validate
our results by assessing gene expression and protein localization in porcine wounds. Aim 2: To determine
whether interactions between dorsal root ganglion fibers and dermal fibroblasts modulate Duroc cutaneous
responses to injury. Our hypotheses for Aim 2 are that 1) genomic differences in Duroc fibroblast responses to
neuroinflammatory signaling cause a fibroproliferative phenotype and 2) Duroc fibroblast-derived signals lead
to increased neurogenesis in Duroc dorsal root ganglion cells. We will use the same approach as in Aim 1. Aim
3: To determine whether differentially expressed Duroc fibroproliferative genes correlate with human
hypertrophic scarring. Our hypothesis for Aim 3 is that differentially expressed genes identified in Aims 1 and 2
have altered expression patterns in human hypertrophic scars and/or have associated single nucleotide
polymorphisms that correlate with severity of human scarring. We will val...

## Key facts

- **NIH application ID:** 9857030
- **Project number:** 5R01GM121369-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** NICOLE SIMONE GIBRAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,338
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857030

## Citation

> US National Institutes of Health, RePORTER application 9857030, Surgical Wound Repair: fibroproliferative responses to cutaneous injury (5R01GM121369-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857030. Licensed CC0.

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