# Keratinocyte Integrin Crosstalk During Wound Healing.

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2020 · $466,249

## Abstract

PROJECT SUMMARY
Epidermal keratinocytes are vital to normal wound healing by restoring the epidermal barrier and secreting
paracrine factors that govern diverse processes including wound angiogenesis and myofibroblast function. In
pathogenic settings, impaired epidermal function results in chronically insufficient (e.g., diabetic ulcers) or over-
exuberant healing (e.g., hypertrophic scars). Our long-term goal is to develop therapeutic paradigms through
which integrins can be manipulated to modulate pathogenic keratinocyte function. While it is well established
that integrins regulate proliferation, migration and growth factor signaling, their roles in orchestrating wound
keratinocyte functions remain enigmatic. Moreover, while normal and wound keratinocytes express integrin
91, in vivo, upon explanation integrin 91 is lost, confounding observations made in previous studies, in
vitro. Using genetically defined, virally transduced keratinocytes that express integrins 31 and/or 91 in
different combinations, we discovered in the last project period that 91 exerts a cross-suppressive effect on
wound cell function and gene expression that is governed by 31, including paracrine signals that promote
endothelial cell function and autocrine signals that regulate basement membrane assembly. Using genetically
defined mice that we have derived expressing different combinations of 31 and/or 91 in the epidermis, we
also found that deletion of 91 from epidermis promoted wound angiogenesis and enhanced laminin 2
processing in the regenerating, epidermal basement membrane after injury. Based on our recently published
studies and new foundation data, we now hypothesize that 91 cross-suppresses 31-dependent
keratinocyte functions through inhibition of a novel 31-FAK-YAP/TAZ signaling axis. We further hypothesize
that this signaling axis controls a gene expression program that promotes keratinocyte wound functions,
including paracrine stimulation of endothelial cells and fibroblasts and autocrine regulation of basement
membrane assembly. This hypothesis will be tested in three Aims using a combination of co-culture models,
qPCR arrays, proteomics, PAC-seq mRNA analysis, cell biology, and defined genetic mouse models. At the
end of this project period, we will have built on the foundation developed in the first project period to elucidate
the complex signaling network downstream of integrin signaling in keratinocytes that governs paracrine and
autocrine signaling in normal wounds. We will also have determined how these integrin signaling pathways are
altered in epidermal tumors in which angiogenesis and other wound processes persist. In doing so, we will
have developed the basis for novel integrin targeting therapeutics to modulate keratinocyte function and wound
outcome.

## Key facts

- **NIH application ID:** 9904471
- **Project number:** 5R01AR063778-07
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** C. Michael DiPersio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,249
- **Award type:** 5
- **Project period:** 2013-02-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904471

## Citation

> US National Institutes of Health, RePORTER application 9904471, Keratinocyte Integrin Crosstalk During Wound Healing. (5R01AR063778-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9904471. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*