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Targeting lysyl oxidase reduces peritoneal fibrosis
Christopher R Harlow1, Xuan Wu1, Marielle van Deemter1
1MRC/University of Edinburgh Centre for Reproductive Health, Edinburgh Medical School, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, United Kingdom.
Plos One
|August 12, 2017
Summary
Targeting lysyl oxidase (Lox) with inhibitors reduced fibrosis and collagen deposition in mice, suggesting a new approach for preventing abdominal adhesions after surgery or disease.
Area of Science:
- Biomedical Research
- Molecular Biology
- Surgical Pathology
Background:
- Abdominal adhesions, pain, and infertility stem from surgery and disease, with excessive collagen deposition as a key factor.
- Current treatments for these conditions are largely ineffective.
- Lysyl oxidase (Lox) is crucial for collagen crosslinking and deposition, making it a potential therapeutic target.
Purpose of the Study:
- To investigate the potential of targeting lysyl oxidase (Lox) as a strategy to reduce abdominal adhesions.
- To explore the role of Lox in fibrosis and collagen deposition in the peritoneum.
Main Methods:
- Mice were induced with fibrosis using multiwalled carbon nanotubes (NT) and treated with Lox inhibitors (BAPN, miRNA), progesterone, or dexamethasone.
- Fibrotic lesions and gene expression in peritoneal mesothelial cells (PMC) were analyzed.
- In vitro studies examined the effect of progesterone on Lox mRNA in cultured PMC.
Main Results:
- Lox inhibitors and steroids significantly reduced NT-induced fibrosis and collagen deposition.
- BAPN and dexamethasone disrupted collagen fiber alignment.
- Steroids inhibited increased expression of fibrosis-related genes (Lox, Col1a1, Col3a1, Bmp1) in PMC; progesterone inhibited IL-1α-induced Lox expression.
Conclusions:
- Targeting peritoneal lysyl oxidase (Lox) shows promise in ameliorating fibrosis and adhesion development.
- This study provides proof-of-concept for Lox inhibition as a therapeutic strategy for abdominal adhesions.
