RESUMO
Hashimoto's thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone's understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.
Assuntos
Quimiocina CCL2/metabolismo , Quimiocina CCL3/metabolismo , Doença de Hashimoto/imunologia , Câncer Papilífero da Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Quimiocina CCL2/análise , Quimiocina CCL3/análise , Feminino , Doença de Hashimoto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Organoides , Cultura Primária de Células/métodos , Proteômica , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
Photomorphogenesis is a critical developmental process bridging light-regulated transcriptional reprogramming with morphological changes in organisms. Strikingly, the chromatin-based transcriptional control of photomorphogenesis remains poorly understood. Here, we show that the Arabidopsis (Arabidopsis thaliana) ortholog of ATP-dependent chromatin-remodeling factor AtINO80 represses plant photomorphogenesis. Loss of AtINO80 inhibited hypocotyl cell elongation and caused anthocyanin accumulation. Both light-induced genes and dark-induced genes were affected in the atino80 mutant. Genome-wide occupancy of the H2A.Z histone variant and levels of histone H3 were reduced in atino80 In particular, AtINO80 bound the gene body of ELONGATED HYPOCOTYL 5 (HY5), resulting in lower chromatin incorporations of H2A.Z and H3 at HY5 in atino80 Genetic analysis revealed that AtINO80 acts in a phytochrome B- and HY5-dependent manner in the regulation of photomorphogenesis. Together, our study elucidates a mechanism wherein AtINO80 modulates nucleosome density and H2A.Z incorporation and represses the transcription of light-related genes, such as HY5, to fine tune plant photomorphogenesis.