Targeting Lysyl Oxidase as a Potential Therapeutic Approach to Reducing Fibrotic Scars Post-operatively: Its Biological Role in Post-Surgical Scar Development

Author:

Sabbagh Mahin Ghorban1,Aliakbarian Mohsen12,Khodashahi Rozita13,Ferns Gordon-A4,Rahimi Hoda1,Ashrafzadeh Kiarash1,Tavakkoli Mahmoud5,Arjmand Mohammad-Hassan1

Affiliation:

1. Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3. Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4. Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK

5. Kidney Transplantation Complication Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Abstract: Abdominal and pelvic surgery, or any surgical injury of the peritoneum, often leads to chronic abdominal adhesions that may lead to bowel obstruction, infertility, and pain. Current therapeutic strategies are usually ineffective, and the pathological mechanisms of the disease are unclear. Excess collagen cross-linking is a key mediator for extra-cellular matrix deposition and fibrogenesis. Lysyl oxidase is a key enzyme that catalyzes the formation of stabilizing cross-links in collagen. Dysregulation of Lysyl oxidase (Lox) expressing upregulates collagen cross-linking, leading ECM deposition. Tissue hypoxia during surgery induces molecular mechanisms and active transcription factors to promote the expression of several genes related to inflammation, oxidative stress, and fibrosis, such as transforming growth factor beta, and Lox. Studies have shown that targeting Lox improves clinical outcomes and fibrotic parameters in liver, lung, and myocardial fibrosis, therefore, Lox may be a potential drug target in the prevention of postsurgical adhesion.

Publisher

Bentham Science Publishers Ltd.

Subject

Clinical Biochemistry,Drug Discovery,Pharmacology,Molecular Medicine

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