# MMP13 expression and function in allergic inflammation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $407,286

## Abstract

PROJECT SUMMARY/ABSTRACT
Atopic dermatitis, asthma, and other allergic diseases pose an enormous socioeconomic burden in the United
States and worldwide. Current treatment options for these illnesses are, however, limited in efficacy and lead
to symptomatic relief in only subsets of patients. More broadly effective therapies against allergic diseases are
desperately needed, yet achieving this imperative requires an advanced understanding of their pathogenic
mechanisms and identification of new therapeutic targets. The protein kinase p38α is expressed in most
mammalian cell types, and activated by a multitude of immunological signals such as microbial stimuli and
cytokines. We have been studying the role of p38α in immunity and inflammation using mice with p38α gene
deficiency in various cell types. These efforts led us to discover that p38α in skin epithelial cells played a
crucial role in driving atopic dermatitis-like inflammation upon allergen challenge. p38α signaling was found to
serve pro-allergic functions via promoting the expression of inflammatory mediators in epithelial cells. We
identified the matrix metalloproteinase MMP13 as an epithelial enzyme whose expression was dependent on
p38α signaling. Importantly, genetic ablation or pharmacological inhibition of MMP13 suppressed allergic skin
and airway inflammation in mice. These findings and other preliminary data suggested the p38α-MMP13 axis
as a promising therapeutic target for allergic diseases. In the proposed research, we will seek to validate the
importance of the p38α-MMP13 axis in allergen-specific immune sensitization and allergic tissue inflammation.
Further, we will perform biochemical analysis of cultured cells and recombinant proteins to establish the
molecular pathways underlying p38α-dependent MMP13 expression and MMP13-mediated inflammatory
responses. To achieve these goals, we will pursue the following specific aims: to determine the role of
epithelial p38α signaling and MMP13 activity in mouse models of atopic dermatitis and asthma (Aim #1); to
elucidate the mechanisms linking p38α signaling to MMP13 expression in skin and airway epithelial cells (Aim
#2); and to identify the proteolytic targets of MMP13 that contribute to regulating allergic inflammation (Aim #3).
The proposed research is expected to reveal the precise pathophysiological functions of p38α and MMP13
during allergic inflammation and the therapeutic potential of targeting the p38α-MMP13 axis in atopic dermatitis
and asthma. The molecular mechanisms newly identified in our study will expand the sphere of knowledge
about cell signaling in allergic disorders.

## Key facts

- **NIH application ID:** 10054652
- **Project number:** 5R01AI127768-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jin Mo Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $407,286
- **Award type:** 5
- **Project period:** 2016-11-22 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054652

## Citation

> US National Institutes of Health, RePORTER application 10054652, MMP13 expression and function in allergic inflammation (5R01AI127768-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10054652. Licensed CC0.

---

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