# Methionine Restriction Attenuates Scar Formation in Fibroblasts Derived from Patients with Post-Burn Hypertrophic Scar

## TL;DR

Methionine restriction reduces scar formation in fibroblasts from burn patients by inhibiting fibrotic pathways and cell activity.

## Contribution

This study is the first to show that methionine restriction can inhibit scar formation in hypertrophic scar fibroblasts.

## Key findings

- Methionine restriction reduced inflammation and suppressed fibroblast proliferation and migration.
- MetR downregulated TGF-β-SMAD, STAT, and AKT/mTOR pathways while upregulating MAPKs.
- MetR promoted apoptosis and reduced extracellular matrix protein secretion in scar fibroblasts.

## Abstract

Methionine restriction (MetR) is a common adjuvant treatment for cancer. However, studies of MetR have paid little attention to its potential implications for fibrosis. Hypertrophic scarring (HTS) is an abnormal fibrotic response after burn trauma that results from the excessive activation of fibroblasts. Because of the absence of a fully effective pharmacological treatment, HTS frequently causes great annoyance in patients as a common sequela of burns. To date, the effects of MetR on hypertrophic scar fibroblasts (HTSFs) remain unclear. This study aimed to investigate the anti-fibrotic effects of MetR and explore the associated alterations in signaling pathways in HTSFs. We isolated HTSFs from post-burn HTS tissues and cultured them in a specially prepared MetR medium. Cell and immunocytochemical staining images were captured using light and fluorescence microscopes, respectively. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. mRNA and protein expression levels were determined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. In HTSFs, MetR reduced cellular inflammation; downregulated multiple signaling pathways, including the TGF-β-SMAD, STAT, and AKT/mTOR pathways; and upregulated MAPKs. Furthermore, MetR arrested the cell cycle, promoted apoptosis, suppressed cell proliferation and migration, and reduced extracellular matrix protein secretion, thereby exerting multifaceted inhibitory effects on HTS. Our results demonstrated that MetR can inhibit scars’ formation and suggest that regulating methionine metabolism in the scar environment may help treat scars.