# Influence of macrophage-fibroblast interactions and mechanotransduction on fibrotic progression

> **NIH NIH F32** · OHIO STATE UNIVERSITY · 2022 · $55,447

## Abstract

Project Summary/Abstract
Idiopathic pulmonary fibrosis is a progressive and non-resolving disease with a median survival of 2-5 years. It
is characterized by restriction of lung expansion during breathing due to excess deposition and remodeling of
the extracellular matrix that prevents gas exchange ultimately causing death. The factors that contribute to
fibrosis progression are multifaceted and include aspects such as extracellular matrix (ECM) remodeling and
deposition, immune cell recruitment and activation, and altered mechanical forces due to changes in the lung
stiffness. Fibroblasts are the main effector cells within fibrosis driving matrix deposition by secreting collagen
and remodeling of ECM architecture. Our group has demonstrated that interactions between fibroblasts and
immune cells, such as macrophages, alter expression of ECM proteins; however, the role of the lung
microenvironment as well as mechanical force in regulating these intracellular interactions is not well understood.
The objective of this work is to establish a next generation in vitro system to examine the impact of tensile force
on cellular interactions of macrophage-fibroblast 3D co-cultures. We hypothesize that the combined factors of
aberrant force stimulation and 3D co-cultures with diseased macrophages will drive fibrotic progression. Aim 1
will assess fibrotic buildup in mechanically stimulated co-cultures through quantification of ECM deposition and
remodeling, changes in gene expression, and functional contractility assays. Aim 2 will then assess fibrotic
resolution via changes in regulation of degradation enzymes and collagen uptake receptors, enzymatic activity
assays, and ECM stiffness changes. This multi-aspect model will provide a more physiological system to study
the collective effects of mechanical stimulation and 3D co-cultures in fibrosis. Fellowship Training Plan and
Environment: It is my long term goal to become a tenure track faculty and researcher in mechanotransduction.
This project will assist me in attaining that goal by providing the technical skills, mentorship and networking
experiences needed to shape me into a well-rounded candidate for application to a K99/R00 award and tenure
track faculty positions.

## Key facts

- **NIH application ID:** 10466105
- **Project number:** 1F32HL164020-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Caymen Novak
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $55,447
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466105

## Citation

> US National Institutes of Health, RePORTER application 10466105, Influence of macrophage-fibroblast interactions and mechanotransduction on fibrotic progression (1F32HL164020-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10466105. Licensed CC0.

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