IGF-1 activated pathways in orbital fibroblasts

Orbital fibroblasts (OFs) are central to thyroid eye disease (TED) pathogenesis. Elevated insulin-like growth factor 1 receptor (IGF-1R) in TED OFs contributes to disease progression, but underlying mechanisms remain unclear. To elucidate IGF-1R-mediated signaling in OFs, we performed RNA-seq analysis after IGF-1 stimulation. Our data reveal that IGF-1 induces gene expression associated with cell proliferation, microtubule dynamics, and lipid metabolism while suppressing cell adhesion, senescence, and chromatin remodeling. Validation studies confirmed upregulation of CRABP2, a key regulator of retinoic acid signaling, and its role in IGF-1-induced OF migration. These findings uncover novel IGF-1R downstream effectors, providing insights into TED pathophysiology and potential therapeutic targets. To better understand the downstream effects of IGF-1 signaling in thyroid eye disease orbital fibroblasts (TED-OFs), unbiased RNA sequencing was performed on two different TED-OF strains treated with IGF-1 (50 ng/mL) or with Vehicle (V) for 24 hours. Samples are in biological replicates (1-3).