TGFβ2-Hepcidin Feed-Forward Loop in the Trabecular Meshwork Implicates Iron in Glaucomatous Pathology.

ABSTRACT:

Purpose

Elevated levels of transforming-growth-factor (TGF)-β2 in the trabecular meshwork (TM) and aqueous humor are associated with primary open-angle glaucoma (POAG). The underlying mechanism includes alteration of extracellular matrix homeostasis through Smad-dependent and independent signaling. Smad4, an essential co-Smad, upregulates hepcidin, the master regulator of iron homeostasis. Here, we explored whether TGF-β2 upregulates hepcidin, implicating iron in the pathogenesis of POAG.

Methods

Primary human TM cells and human and bovine ex vivo anterior segment organ cultures were exposed to bioactive TGF-β2, hepcidin, heparin (a hepcidin antagonist), or N-acetyl carnosine (an antioxidant), and the change in the expression of hepcidin, ferroportin, ferritin, and TGF-β2 wa

SUBMITTER: Ashok A 

PROVIDER: S-EPMC7401420 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature