# Role of osteopontin in innate immunity during infections and inflammation

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $467,816

## Abstract

PROJECT SUMMARY/ABSTRACT 
Osteopontin (OPN) is involved in the pathogenesis of a wide variety of inflammatory disorders, including
infections, autoimmune diseases, cancer, and other diseases accompanied with inflammation. OPN is primarily
considered to be a pro-inflammatory molecule and is generally known to induce immune responses. However,
recent studies suggested that OPN occasionally functions as an anti-inflammatory molecule, and how OPN
switches its role is entirely elusive. It is critical to know how OPN plays the two-sided role, particularly because
OPN attracts attentions as a pharmaceutical target and a disease marker in various diseases. To this end, this
proposed study seeks to understand the molecular mechanism by which OPN switches immune responses,
and will verify the mechanistic hypothesis with in vivo animal disease models using five lines of OPN mutant
mice.
Our central hypothesis is: Intracellular OPN (iOPN) is a major player to make OPN’s role switch between pro-
inflammatory and anti-inflammatory. Here, OPN has two OPN isoforms, secreted (sOPN) and intracellular
(iOPN). In the past, we first succeeded to biochemically confirm the presence of iOPN, and revealed the
mechanism of iOPN’s generation and its functions. As a pioneer of the iOPN field, we have been continuously
discovering new roles of iOPN, as well as those of sOPN. To study OPN in an isoform-specific fashion, it is
important to have cells and mouse lines that exclusively express one of two isoforms. We are currently
equipped not only with iOPN and sOPN expression vectors, but we will use multiple lines of OPN mutant mice,
which make it possible for us to evaluate the isoform-specific role of OPN in in vivo disease models.
The objective of this proposed study is to determine how iOPN functions as an anti-inflammatory molecule; and
the long-term goal of this project is to elucidate the roles of iOPN and sOPN in inflammation.

## Key facts

- **NIH application ID:** 9875422
- **Project number:** 5R01AI088100-09
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mari L. Shinohara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $467,816
- **Award type:** 5
- **Project period:** 2011-02-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875422

## Citation

> US National Institutes of Health, RePORTER application 9875422, Role of osteopontin in innate immunity during infections and inflammation (5R01AI088100-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9875422. Licensed CC0.

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