# The function of mTORC1/Stat3 signaling in the regulation of fibrovascular scar formation during tendon healing

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $357,500

## Abstract

Project Summary/Abstract
Tendon injuries are challenging clinical problems due to slow, incomplete healing with fibrovascular scar
formation, which reduces tendon function and causes chronic complications such as pain and tendon ruptures.
The limited understanding of the regulatory mechanisms underlying fibrovascular scar formation is a significant
gap in knowledge, hindering the development of effective treatment modalities for tendon diseases.
Fibrovascular scar tissue is characterized by a disorganized extracellular matrix (ECM) with high cellularity and
neovascularization. Therefore, there is a critical need to understand the key factors regulating tendon cells and
ECM maturation during tendon healing to develop regenerative medicine. Recent studies have demonstrated
that mTORC1 (mechanistic target of rapamycin complex 1) signaling is a critical regulator for postnatal tendon
maturation and is associated with pathogenic tendon conditions such as fibrotic adhesion of flexor tendon, fatty
infiltration after rotator cuff tears, and human tendinopathy. However, the function of mTORC1 in fibrovascular
scar formation and its downstream molecular mechanisms are not known. Stat3 (signal transducer and
activator of transcription 3) is involved in fibrotic scar formation in multiple tissues and is known as a
downstream target of mTORC1 signaling in cancer cells. However, there is no reported evidence showing that
Stat3 mediates the function of mTORC1 in fibrovascular scar formation in tendons. Our overall objective is to
define the function of the mTORC1/Stat3 signaling cascade in fibrovascular scar formation and evaluate the
beneficial effects of mTORC1/Stat3 modulation on regenerative tendon healing. The central hypothesis of the
proposed research is that (i) injury-induced mTORC1 signaling governs fibrovascular scar formation during
tendon healing, and (ii) Stat3 mediates mTORC1 function in fibrovascular scar formation via regulation of ECM
organization. We will test the hypothesis using innovative multidisciplinary approaches, including mouse
genetics, a surgical injury model, advanced molecular/imaging analyses, and a biomechanical test. The goal of
Aim1 is to determine the function of mTORC1 in fibrovascular scar formation during tendon healing. The goal
of Aim2 is to define Stat3 as a mediator of mTORC1 function in fibrovascular scar formation in tendons. The
success of the proposed research will significantly advance the mechanistic understanding of fibrovascular
scar formation during tendon healing and provide a new platform to develop translational and clinical
researches targeting the mTORC1/Stat3 signaling cascade for the treatment of debilitating tendon diseases.

## Key facts

- **NIH application ID:** 10444013
- **Project number:** 1R01AR079486-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Kyu Sang Joeng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $357,500
- **Award type:** 1
- **Project period:** 2022-02-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444013

## Citation

> US National Institutes of Health, RePORTER application 10444013, The function of mTORC1/Stat3 signaling in the regulation of fibrovascular scar formation during tendon healing (1R01AR079486-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10444013. Licensed CC0.

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