# MicroRNA-10a in Airway Smooth Muscle and Asthma

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $554,036

## Abstract

PROJECT SUMMARY
Over 300 million people, many of them children, suffer from asthma. Airway smooth muscle
(ASM) controls airway narrowing and plays a pivotal role in the pathogenesis of asthma.
Asthmatic ASM becomes hyper-proliferative, secretes more inflammatory cytokines/chemokines
and may be more contractile. These phenotypic changes in ASM contribute directly to airway
remodeling and airway hyperresponsiveness (AHR)—cardinal features of asthma. Despite
extensive studies on the regulatory mechanisms governing ASM phenotypes, no single gene or
pathway is known to control multiple ASM phenotypes. Consequently, mainstay asthma
therapies reduce either ASM contractility (-agonists) or airway inflammation (glucocorticoids),
and there is no therapy that directly targets ASM proliferation. MicroRNAs are small yet powerful
gene tuners: a single microRNA is capable of targeting a multitude of genes and thus has the
potential to impact diverse cellular processes. We recently identified miR-10a as a highly ASM-
enriched and the most abundant microRNA—accounting for more than 20% of total microRNA
expression in the ASM. We have reported that miR-10a inhibits the proliferation of ASM cells by
directly targeting PI3KCA--the central component of the PI3K pathway. Preliminary data indicate
that miR-10a also suppresses NFB signaling while increasing the expression of 2-adrenergic
receptor (2AR)—the target of mainstay asthma drug -agonists. Importantly, miR-10a
expression is reduced in asthmatic ASM cells and by inflammatory cytokines. Based on these
studies, we hypothesize that miR-10a regulates multiple critical ASM phenotypes via
suppression of specific target genes and that perturbation of this regulation contributes
to the development of asthma and alters response to asthma therapies. To test this
hypothesis, we propose this highly integrative project that combines in vivo mouse models,
molecular mechanistic studies in primary ASM cells, and genetic epidemiology in human
asthma populations. Aim 1 will determine whether miR-10a inhibits AHR by suppressing ASM
proliferation and chemokine secretion. Aim 2 will investigate whether that miR-10a augments
bronchoprotection by inhibiting 2AR downregulation. Aim 3 will determine the association and
function of miR-10a and target gene variants in asthma and in the response to asthma therapy.
Results from this study will establish miR-10a as a master regulator of multiple critical ASM
phenotypes and identify microRNA-10a as a novel therapeutic target for asthma.

## Key facts

- **NIH application ID:** 9837475
- **Project number:** 5R01HL139496-03
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Quan Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $554,036
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837475

## Citation

> US National Institutes of Health, RePORTER application 9837475, MicroRNA-10a in Airway Smooth Muscle and Asthma (5R01HL139496-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9837475. Licensed CC0.

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