Canonical and Truncated Transglutaminase-2 Drive TGF-β1 Autocrine Loop to Induce Fibrosis in Graves' Orbitopathy.

ABSTRACT:

Purpose

To evaluate the role of transglutaminase 2 (TGM2) in fibroblasts of Graves' orbitopathy (GO) and explore its potential mechanisms in orbital fibrosis.

Methods

A key gene selection model for GO was established through bioinformatics and machine learning. Orbital fibroblasts (OFs) were cultured from orbital connective tissue samples. Subsequently, three-dimensional spheroid models were developed. Lentiviral transduction was used to establish TGM2 overexpression and knockdown models. Fibrosis levels were assessed using Western blot, PCR, and collagen contraction assays. TGM2 activity was evaluated by FITC-cadaverine staining and the colorimetric assay. The canonical and truncated TGM2 isoforms were selectively introduced to restore expression. TGF-β1 levels in cell cult

SUBMITTER: Bao X 

PROVIDER: S-EPMC12110627 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature