Study On The Mechanism Of Orbital Fat Tissue Hyperplasia In Thyroid-associated Ophthalmopathy

Purpose: This study aims to clarify possible therapeutic targets during the remodeling of orbit tissue by analysis of m RNA expression for inactive thyroid-associated ophthalmopathy(TAO)patients with proptosis.Methods: Using transcriptome sequencing,we characterized the transcriptional changes in orbital adipose tissue,where orbital adipogenesis.Differentially expressed genes(DEGs)were identified between inactive patients with proptosis and healthy controls.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were conducted to determine biological functions and signaling pathways of the DEGs.The top-ranked genes were selected to be validated by RT-qPCR in orbit fat tissues and orbital fibroblasts.Results: We identified 468 DEGs.The DEGs were enriched in PPAR signaling pathway,regulation of lipolysis in adipocytes,fatty acid metabolism,ECM-receptor interaction,and protein digestion and absorption.The relative expressions of C5,WNT4,WNT1,and COL12A1 were significantly different between orbit fat tissues from TAO and controls,but not significantly different in orbital fibroblasts between two groups.Conclusions: Wnt signaling pathway,C5 and the changes expression of COL12A1 serve as the potential therapeutic targets for TAO,which have the value for further research.Our study sheds new light on the mechanisms underlying TAO pathogenesis.