# The Lipofibroblast to Myofibroblast Transition in Systemic Sclerosis

> **NIH NIH K38** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $110,959

## Abstract

PROJECT SUMMARY/ABSTRACT
Systemic sclerosis (SSc) is a rare autoimmune fibrosing disease that affects 24.4/100,000 people in the United
States. While rare, SSc has the highest mortality of all rheumatologic diseases. The complication most
associated with this high mortality is interstitial lung disease (ILD). Despite this, there remain limited treatments
for systemic sclerosis associated interstitial lung disease (SSc-ILD), and the treatments that do exist only slow
but do not reverse ILD. To create new and better treatments for SSc-ILD, we need to better understand the
mechanisms that drive fibrosis. A previous study showed that myofibroblasts (the cells that drive fibrosis
through the production of extracellular matrix) are derived from lipofibroblasts in a mouse model of interstitial
lung disease. Thus, the lipofibroblast to myofibroblast transition in systemic sclerosis may represent a novel
target for treatment. To date, however, the mechanisms involved in this transition are not well understood. One
known player in the lipofibroblast to myofibroblast transition is PPARg (peroxisome proliferator activated
receptor gamma), a master regulator of lipid metabolism and adipogenesis. PPARg has been shown to be
downregulated during the lipofibroblast to myofibroblast transition and PPARg agonists reduce fibrosis in
mouse models of ILD. In this proposal, we aim to define the mechanisms through which PPARg is itself
regulated allowing for the lipofibroblast to myofibroblast transition to occur. We will do this by using a
multiomics approach to examine the expression and chromatin accessibility of two genes, PER3 (period
circadian protein homolog 3) and CD36 (cluster of differentiation 36), that we believe function upstream and
downstream of PPARg respectively. In Aim 1 of this proposal, we will identify the transitional cell stage during
which lipofibroblasts are transitioning to myofibroblasts and in Aim 2, we will characterize the role of PER3 and
CD36 in the lipofibroblast to myofibroblast transition. Based on previous studies that have defined their roles in
adipogenesis (PER3) and fibrosis (CD36), we hypothesize that PER3 inhibits PPARg transcriptional function
during the lipofibroblast to myofibroblast transition and that downregulation of PPARg during this transition
leads to decreased CD36 expression. Importantly, the use of multiomics allows for an unbiased approach so
that we are not limited to exploring changes in gene expression and chromatin accessibility during this
transition in one candidate at a time. The proposed research builds upon my background in lipid metabolism
research during my time on the R38. The experiments outlined in this proposal will take place at UCLA where I
will have access to necessary equipment and core facilities such as the UCLA Tissue Pathology Core
Laboratory and the UCLA Technology Center for Genomics and Bioinformatics to support the successful
completion of my proposed research. In addition, through my car...

## Key facts

- **NIH application ID:** 10950562
- **Project number:** 1K38HL175027-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Arissa C Young
- **Activity code:** K38 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $110,959
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950562

## Citation

> US National Institutes of Health, RePORTER application 10950562, The Lipofibroblast to Myofibroblast Transition in Systemic Sclerosis (1K38HL175027-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10950562. Licensed CC0.

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