# Pericyte reprogramming in fibrosis

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $483,251

## Abstract

Prior to clinical evidence of fibrosis, microvascular injury occurs, presenting as an altered functional state of the
endothelium, increased permeability, enhanced vasoreactivity, increased expression of adhesion molecules,
excessive inflammation, and altered vascular wall growth. Microvascular rarefaction, or capillary dropout, is
coincident with chronic fibrosis, and considered an accelerator of the disease. However little is known about the
microvascular contribution to fibrotic diseases in which microvasculature are key to tissue health and
homeostasis. Given the central role of the vasculature in barrier function, inflammatory regulation and interstitial
tissue necrosis, it is likely that the microvasculature, specifically, mural perivascular cells (pericytes), are key
contributors to fibrotic development and progression. Recent evidence suggests that microvascular dysfunction
may be more directly influential to tissue remodeling than epithelial cells. Limited availability of human pericytes
from a readily available human source has led to an incomplete understanding of the mechanisms underlying
pericyte to myofibroblast transition that facilitate both microvascular and interstitial matrix remodeling. Our work,
supported by that of others in this area, has led us to the hypothesis that pericytes cease homeostatic
maintenance of the microvasculature by transition into a myofibroblast through the process of
dedifferentiation and re-differentiation known as cellular reprogramming. As myofibroblasts, cells of
pericyte lineage contribute to interstitial tissue fibrosis. Through three distinct aims we will show that, in
response to growth factor, pericytes deposit extracellular matrix proteins to alternatively support vascular stability
and fibrosis as they undergo phenotypic transition from microvascular pericytes to interstitial myofibroblasts. We
also determine points in pericyte transition that may be key for therapeutic intervention. We utilize traditional
molecular biology methods and biomaterials technology to determine the profibrotic mediators promote
functional and phenotypic shifts in pericytes. Using 2- and 3-D bioengineered mechanically and biochemically
tunable polymer based extracellular matrices, we decouple the role of biochemical and mechanical signals in
regulation of PC to myofibroblast transition through the process of reprogramming. Results acquired through use
of human cells in bioengineered structures will be validated with animal models of pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10896140
- **Project number:** 5R01EB033917-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Anjelica Gonzalez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,251
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896140

## Citation

> US National Institutes of Health, RePORTER application 10896140, Pericyte reprogramming in fibrosis (5R01EB033917-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10896140. Licensed CC0.

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