# Role of p120-catenin in sepsis-induced lung injury

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Role of p120-catenin in sepsis-induced lung injury
The overarching theme of this project is the delineation of the novel immunomodulatory function of p120-
catenin (p120) in resolving lung injury and inflammation. The crucial observations underpinning this renewal
proposal (presented in Supporting Data) suggest an essential host-defense function of p120 expression in
macrophages in regulating clearance of apoptotic neutrophils (efferocytosis). We observed that loss of p120
expression in macrophages severely impaired the ability of macrophages to phagocytose the apoptotic
neutrophils. Specific p120 ablation in macrophages markedly delayed recovery of inflammatory lung injury in a
murine model of sepsis. These results raise several fundamental questions central to lung’s host-defense
function that will be addressed in this proposal, including: How does p120 regulate the phagocytosis of
apoptotic neutrophils? Is this p120-mediated function required for resolving inflammatory lung injury? Can
pulmonary transplantation of genetically engineered macrophage expressing p120 accelerate repair of lung
injury? Although p120 is a well-described constituent of adherens junctions in epithelial and endothelial cells,
our studies during the previous cycle of the grant have demonstrated that endothelial p120 protected the lungs
from sepsis-induced injury by inhibiting Toll-like receptor 4 signaling. In this renewal proposal, we will focus on
defining previously unrecognized function of p120 in pulmonary macrophages and whether it orchestrates
resolution of inflammation and lung repair and, if so, the underlying mechanisms mediating this action of p120.
Thus we will test the central hypothesis that p120 in pulmonary macrophages favors resolution of
inflammatory lung injury by modulating efferocytosis-related signaling. This hypothesis will be tested by
addressing the following Specific Aims. In Aim 1, we will define the molecular mechanisms by which p120
regulates the ability of pulmonary macrophages to phagocytize apoptotic neutrophils. In Aim 2, we will
evaluate the functional significance of pulmonary macrophage p120 as an essential protein in the resolution
mechanism of inflammatory lung injury. We hope through these studies to provide important and useful
insights into the role of p120 in the pathogenesis of lung injury and in the repair processes. With the completion
of these studies, we will have a more clear understanding of the role of pulmonary macrophage p120 as a
potentially important and novel modulator of lung immune function and also as a potential therapeutic target to
promote resolution of inflammatory lung injury.

## Key facts

- **NIH application ID:** 9959490
- **Project number:** 5R01HL104092-10
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Guochang Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2010-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959490

## Citation

> US National Institutes of Health, RePORTER application 9959490, Role of p120-catenin in sepsis-induced lung injury (5R01HL104092-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9959490. Licensed CC0.

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