# Role of TSG-6 mediated hyaluronic acid cross-linking in acute lung injury

> **NIH NIH F30** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $50,520

## Abstract

PROJECT SUMMARY
Changes to the extracellular matrix (ECM) help direct the inflammatory response to tissue injury and resolution
of inflammation. During inflammation, TNF-stimulated gene-6 (TSG-6) covalently modifies the ECM
polysaccharide hyaluronic acid (HA) with the heavy chains (HCs) from the serum protein inter-alpha-inhibitor
(IαI). This cross-linking of HA is exclusively carried out by TSG-6 and only occurs during tissue injury, where
inflammatory mediators are present to induce TSG-6 secretion and leaky vessels allow serum IαI to enter
tissue. While HA cross-linking is present in histopathological lesions of various chronic lung diseases, the
presence and role of TSG-6 mediated cross-linking in acute lung injury remains undefined. This proposal will
establish for the first time the role of HA cross-linking in directing leukocyte recruitment and delaying resolution
during acute lung inflammation. The clinically relevant murine model of Pseudomonas aeruginosa (PA)
induced acute lung injury and repair will be used to test the hypothesis that TSG-6 mediated HA cross-linking
mediates the recruitment of pro-inflammatory macrophages to the airway (Aim 1) and prolongs inflammation
(Aim 2). In Aim 1, we will utilize mice deficient for TSG-6 and IαI as well as TSG-6 supplementation in IαI mice
to specifically determine the role of TSG-6 mediated HA cross-linking in the recruitment of pro-inflammatory
macrophages. In Aim 2, we will utilize TSG-6 loss of function approaches (TSG-6 null mice and neutralization
antibody) to determine the effect of inhibiting TSG-6 on the rate of epithelial repair following PA infection.
Completion of these aims will establish a new understanding of the role of TSG-6 induction in the lung and its
evolutionarily conserved modifying of HA during inflammation that may yield new therapeutic strategies for lung
repair.

## Key facts

- **NIH application ID:** 9860936
- **Project number:** 5F30HL136169-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Kevin Ni
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9860936

## Citation

> US National Institutes of Health, RePORTER application 9860936, Role of TSG-6 mediated hyaluronic acid cross-linking in acute lung injury (5F30HL136169-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9860936. Licensed CC0.

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