# The Matricellular Protein CCN1 in Wound Healing

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $415,605

## Abstract

PROJECT SUMMARY
In an environment replete with microbial invaders, mammals must mount a successful defense against
microbes in cutaneous wounds, trauma, and tissue injury. Staphylococcus aureus and Pseudomonas
aeruginosa are the most common bacteria isolated from chronic skin wounds and among the most
prominent pathogens in community-acquired and nosocomial infections, and these organisms readily
develop antibiotic resistance. The matricellular protein CCN1 has recently emerged as an important
multifunctional regulator of the wound healing process. CCN1 directly induces myofibroblast senescence
through integrin α6β1 in the maturation phase of wound repair, thereby initiating matrix remodeling and
dampening fibrosis. Recent studies have uncovered additional unexpected but critical activities of CCN1 in
wound repair: (1) CCN1 acts as a bridging molecule and triggers the phagocytic removal of apoptotic
neutrophils in wounds, resulting in resolution of inflammation and allowing healing to proceed. (2) CCN1
promotes clearance of S. aureus and P. aeruginosa by inducing their phagocytosis by macrophages and
neutrophils. Bacterial clearance is impaired in knockin mice expressing a CCN1 mutant unable to bind
integrin αvβ3/αvβ5, and accelerated in mice injected with purified CCN1 protein. Moreover, treatment of
excisional wounds with purified CCN1 protein accelerates closure in diabetic mice. Based on these findings,
we hypothesize that CCN1 is a multifunctional protein that regulates disparate aspects of wound healing,
including clearance of infecting microbes, resolution of inflammation, and indirectly lead to enhanced
granulation tissue formation. We will scrutinize this hypothesis in three specific aims: Aim 1 evaluates the
role of CCN1 in bacterial clearance in animal models of infection; Aim 2 dissects the molecular mechanism
of CCN1 action in bacterial clearance; and Aim 3 investigates how CCN1 accelerates diabetic wound
healing. Together, these studies will illuminate the mechanism of a novel arsenal in innate immunity against
microbial invaders and may prompt new approaches toward the management of antibiotic-resistant
infections and chronic non-healing wounds.

## Key facts

- **NIH application ID:** 9944451
- **Project number:** 5R01AR061791-09
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** LESTER F LAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,605
- **Award type:** 5
- **Project period:** 2011-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944451

## Citation

> US National Institutes of Health, RePORTER application 9944451, The Matricellular Protein CCN1 in Wound Healing (5R01AR061791-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944451. Licensed CC0.

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