Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids.

ABSTRACT:

Background

Uterine fibroids are highly prevalent, collagen-rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth. We also used two FDA-approved drugs, verteporfin and nintedanib, to elucidate the role of Hippo/YAP signaling in uterine fibroid and myometrial cells.

Methods

The clinical trial was registered (NCT02889848).

SUBMITTER: Islam MS 

PROVIDER: S-EPMC8255059 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature