# The mechanistic role of surfactant protein A in smooth muscle cell phenotype modulation and vascular remodeling

> **NIH NIH F32** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $67,032

## Abstract

PROJECT SUMMARY
The overall goal of this proposal is to find novel mechanisms whereby surfactant protein A (SPA)
regulates vascular smooth muscle cell (SMC) phenotype modulation. SMC transition from a
differentiated to dedifferentiated phenotype in addition to neointima formation/vascular remodeling has
a critical role in human diseases such as the development of atherosclerosis, restenosis after
angioplasty or bypass, diabetic vascular complications, arteriopathy transplants, asthma and cancer.
Mechanisms that regulate SMC phenotype modulation and neointima formation are not well
understood. The physiological function of SPA is its secretion by type II alveolar cells to maintain
minimal surface tension in the lungs. However, preliminary data indicate a role for SPA as a SMC
phenotype modulator. In vivo, SPA was expressed in the medial and neointimal SMCs following
mechanical injury in rat and mouse carotid arteries. The wire-injury induced intimal hyperplasia was
dramatically attenuated in SPA knockout mice. Furthermore, increased mRNA expression of SMC
contractile genes and key regulators for contractile SMC phenotype, Myocardin and TGF-β1 was
observed in SMCs isolated from SPA knockout mice. Additionally, SMCs from SPA knockout mice had
increased Smad3 phosphorylation and the increase was blocked by the TGF-β1 neutralizing antibody.
SPA is localized in the nucleus of SMCs suggesting it may have a role in SMC gene transcription.
Indeed, SPA deficiency increased smooth muscle α-actin and smooth muscle 22-α promoter activity
whereas recombinant SPA protein attenuated their activities. Hence, the central hypothesis is that
SPA regulates SMC phenotype modulation and vascular remodeling through both extracellular (via
modulating TGF-β1 signaling) and intracellular (Myocardin-related gene transcription) mechanisms.
Using primary culture of SMC, in vivo mouse wire injury models combined with molecular, cellular and
histological approaches, this proposal will 1) determine the molecular extracellular and intracellular
mechanisms by which SPA regulates SMC phenotypic modulation; and 2) determine if SPA is essential
for SMC phenotype modulation/vascular remodeling in vivo. Project completion will uncover novel
mechanisms regulating SMC phenotypic modulation and provide understanding into whether SPA is a
potential target for therapy against vascular damage associated with common vascular diseases such
as diabetes, restenosis, atherosclerosis and cancer. The training plan laid out by the sponsor and the
outstanding environment in the mentor’s laboratory and at the University of Missouri will safeguard the
successful completion of the proposed studies.

## Key facts

- **NIH application ID:** 10313259
- **Project number:** 1F32HL159930-01
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Skylar Dawn King
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $67,032
- **Award type:** 1
- **Project period:** 2021-09-10 → 2024-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313259

## Citation

> US National Institutes of Health, RePORTER application 10313259, The mechanistic role of surfactant protein A in smooth muscle cell phenotype modulation and vascular remodeling (1F32HL159930-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10313259. Licensed CC0.

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