# SOCS domain-mediated fibronectin matrix degradation on fibrosis reversal

> **NIH NIH R15** · NORTHERN ARIZONA UNIVERSITY · 2021 · $469,034

## Abstract

ABSTRACT
Idiopathic Pulmonary fibrosis (IPF) is an irreversible lung disease with no effective treatment options.
Insurance claims data on IPF incidence between years 2001-2011 was estimated at 31-43 per 100,000 per
year, translating to 89,000 patients living with IPF in the United States in the year 2000 and 34,000 new cases
diagnosed per year. IPF is a disease of unknown etiology and myriad environmental factors are known to
contribute to the development of the disease in susceptible individuals. During fibrosis, fibroblasts differentiate
into myofibroblast cells that produce vast amounts of extracellular matrix (ECM) proteins that alter matrix
rigidity and lung architecture impacting lung function. A critical constituent of the ECM is the core matrisome
protein fibronectin (FN) that assembles into a FN matrix contributing to Collagen matrix formation and ECM
rigidity. Von Hippel Lindau (VHL) protein is required for the FN matrix formation and is upregulated in the lungs
of IPF patients. We have shown that the SOCS domain (Suppressors Of Cytokine Signaling), a 40 amino acid
conserved domain in the SOCS family of proteins, targets VHL for degradation by a cullin-dependent ubiquitin
ligase mechanism. We hypothesize that SOCS domain overexpression in myofibroblasts will result in
degradation of the pathologic FN matrix in myofibroblasts and fibrosis reversal. We will perform these
experiments using lung fibroblasts transduced with the SOCS domain and the SOCS domain mutant that is
defective in VHL degradation. Using RNAseq and phosphoproteome analysis, we will develop a computational
pipeline to identify probable signaling mediators in the process of myofibroblast reversal. Our in vitro findings,
will be evaluated in a Bleomycin-induced in vivo mouse model of lung fibrosis to test the efficiency of fibrosis
reversal by adenoviral-mediated delivery of the SOCS domain. We expect a reduction of fibrosis markers in
our in vitro experiments and significant reversal of fibrosis in our in vivo model. The results from these
experiments will offer new peptide based targets as well as provide therapeutic agents that can be used either
on its own or in combination with existing therapies to reverse matrix formation and fibrosis.

## Key facts

- **NIH application ID:** 10292074
- **Project number:** 1R15HL154051-01A1
- **Recipient organization:** NORTHERN ARIZONA UNIVERSITY
- **Principal Investigator:** JANI CHERI INGRAM
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $469,034
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292074

## Citation

> US National Institutes of Health, RePORTER application 10292074, SOCS domain-mediated fibronectin matrix degradation on fibrosis reversal (1R15HL154051-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10292074. Licensed CC0.

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