# Altered Mechanosensing by Oral Mucosal Fibroblasts Inhibits the Myofibroblast Transition

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $255,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Unlike the dermis, the oral cavity is a site of privileged healing that does not significantly scar. Based on limited
data, oral mucosal wound healing has been suggested as a model for exploring mammalian regeneration. In
particular, oral mucosal fibroblasts exhibit unique characteristics when compared to dermal fibroblasts
suggesting that these cells are programmed to facilitate scarless healing. Many parallels have been drawn
between the oral mucosa and fetal skin which can also heal without scar formation. Oral mucosal fibroblasts
share several characteristics with fetal dermal fibroblasts which have been recognized as a key component of
scarless repair. Injured skin in the mammalian fetus heals scarlessly without myofibroblast involvement
suggesting that smaller cellular forces contribute to regenerative repair. In vivo and in vitro studies have shown
that fetal fibroblasts have unique characteristics that contribute to scarless healing including altered responses
to ECM rigidity and defective signaling pathways. However, it is unknown whether oral mucosal fibroblasts also
demonstrate this distinct phenotype and exhibit differential responses to environmental mechanical factors that
induce myofibroblast differentiation in postnatal or “adult” dermal fibroblasts which would represent a novel
avenue of research for uncovering new mechanisms that drive scarless healing. Therefore, we hypothesize
that oral mucosal fibroblasts have intrinsically altered mechanosensing mechanisms that limit their
ability to transition into myofibroblasts. We will test this hypothesis in the following Specific Aims: (1) test
the hypothesis that oral mucosal fibroblasts respond to physiologic biomechanical rigidities with an attenuated
contractile response and (2) identify molecular differences in oral mucosal fibroblasts that can be targeted to
reduce myofibroblast differentiation in adult dermal fibroblasts. We are taking an innovative approach by
utilizing the mechanical phenotype of oral mucosal fibroblasts as a model for understanding regenerative
repair. We will test our novel concept by using synthetic and biological substrates that mimic the different
mechanical stages of wound healing that progressively induce myofibroblast differentiation to isolate the
effects of physiologic rigidities. Overall, our goal is to delineate the underlying molecular and physical
mechanisms by which oral mucosal fibroblasts may differentially mechanosense ECM rigidity by quantifying
cellular biomechanical properties relevant to tissue repair. Furthermore, our research plan is designed to
uncover potential molecular targets for novel treatment strategies for dermal scarring and fibrosis in postnatal
wound healing. These studies are of particular clinical importance since no acceptable anti-fibrotic therapies
currently exist and dermal scarring and fibrosis costs billions of dollars of year in medical care and
management. In addition, the expected outcomes...

## Key facts

- **NIH application ID:** 9985796
- **Project number:** 5R21DE029002-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Aron Parekh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $255,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985796

## Citation

> US National Institutes of Health, RePORTER application 9985796, Altered Mechanosensing by Oral Mucosal Fibroblasts Inhibits the Myofibroblast Transition (5R21DE029002-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9985796. Licensed CC0.

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