A systematic review of the role and expression of TGF-Beta in uterine fibroids

 

Objective: Transforming Factor-Beta (TGF-Beta) plays a key role in fibroid development and may be a key therapeutic target. This review aims to evaluate current understanding of the expression of TGF-Beta in uterine fibroids.

 

 Methods: A comprehensive search across PubMed, Embase and MEDLINE identified 537 studies comparing TGF-Beta levels in leiomyoma versus myometrial tissue. Following a predefined inclusion and exclusion criteria, 28 studies were included for review.

 

 Results:

 

- TGF-Beta isoforms: 8 studies showed no or reduced expression of TGF-Beta1; 4 found overexpression. 18 studies found overexpression of TGF-Beta3 highlighting its role in extracellular matrix (ECM) production. No difference was observed in TGF-Beta2

 

- Therapeutics: Treatments such as Ulipristal acetate and Vitamin D were linked to a reduction in TGF-Beta via Smad and Non-Smad pathways. Factors regulating TGF-Beta included ovarian hormones, Wnt/Beta-Catenin pathway, MED12 mutation and ECM-related microRNAs.

 

- Biomarker potential: 2 studies measuring TGF-Beta in serum suggest its use in diagnosis and monitoring providing an alternative use to the cytokine.

 

Conclusion: TGF-Beta is central to fibroid pathogenesis and is a viable drug target. Further research is needed on the multi-omic causes of fibroids, on the use of combination therapies and the complete mechanisms involved in fibroid development.