# The regulatory roles of nuclear SM22 in smooth muscle phenotypic modulation

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $522,174

## Abstract

Project Summary: Vascular smooth muscle cell (SMC) phenotypic modulation plays critical roles in the
pathogenesis of vascular diseases. SRF (Serum Response Factor) is a critical transcription factor that plays a
central role in regulating gene transcription in SMC phenotypic modulation by competitively binding with
Myocardin (the key differentiation regulator) and other key transcription regulators such as Elk and NF-kB.
Extensive studies have characterized the mechanisms of actin-Myocardin interaction in SRF-mediated
transcription, yet surprisingly the question of whether actin directly targets SRF to modulate SMC differentiation
and phenotypic modulation has not been addressed. Downregulation of actin cytoskeleton proteins including
actin and SM22 (an actin binding protein) has long been recognized as a marker of SMC phenotypic
modulation and was until now regarded as a consequence of SMC dedifferentiation. However, we have now
accumulated compelling evidence suggesting that SM22 but not actin can target SRF to regulate its
transcriptional activities. The goal of this project is to characterize the molecular mechanisms of SM22 in
coordinatively regulating the transcription of a variety of genes involved in SMC modulation from contractile
phenotype to pathogenic phenotypes. Based on our published work and exciting preliminary results, we
hypothesize that SM22 regulates SMC phenotypes as a transcription cofactor to modulate the interplay of SRF
and other key transcription regulators for SMC differentiation and dedifferentiation in the vessel wall. We will
take the system biology approach using integrated molecular, cellular, genetic, and bioinformatics methods to
test this hypothesis. The Specific Aims are (i) to determine the molecular mechanisms whereby SM22
regulates the function of SRF in SMC phenotypic modulation in cultured SMCs. (ii) to determine the roles of
SM22 in the pathogenesis of vascular wall remodeling in response to vascular injury using knockout and
transgenic mice generated in our lab. Successful completion of this project will likely validate a new paradigm
whereby actin cytoskeleton proteins actively participate in regulating smooth muscle phenotypic modulation
during the pathogenesis of vascular diseases. We expect that the proposed studies will have the positive
impact of identifying cytoskeleton proteins as a new class of targets for future pharmaceutical intervention.

## Key facts

- **NIH application ID:** 9978091
- **Project number:** 5R01HL142956-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** LI LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $522,174
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978091

## Citation

> US National Institutes of Health, RePORTER application 9978091, The regulatory roles of nuclear SM22 in smooth muscle phenotypic modulation (5R01HL142956-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978091. Licensed CC0.

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