Depressive Mood Promotes the Occurrence and Development of Thyroid Nodules Through the(IL-6,TNF-α,IL-1β)/JAK2/STAT3/VEGF Pathway

WANG Changlin; QIAO Mingqi; GAO Dongmei; GUO Yinghui; WANG Jieqiong; SONG Chunhong

doi:10.3969/j.issn.1006-3250.2025.10.018

Abstract：Objective To explore the mechanisms by which depressive mood promotes the development of thyroid nodules.Methods Potential key signaling pathways were predicted and screened through network database analysis and literature review.Animal experiments were conducted for validation:rats were randomly divided into a blank group,a propylthiouracil(PTU)group,and a chronic unpredictable mild stress(CUMS)+PTU group.The blank and PTU groups were housed socially,while the CUMS+PTU group was isolated and subjected to CUMS modeling for 6 weeks.Except for the blank group,which received an equal volume of 0.9%sodium chloride solution by gavage,the other groups were administered 0.1%PTU solution once daily at 10 mL/kg for 6 weeks.Behavioral tests were used to evaluate emotional status.Ultrasound imaging,morphological observation,pathological staining,and serum hormone detection were employed to comprehensively assess the effects of depressive mood on thyroid nodule formation.Protein levels of key factors in the screened signaling pathway were measured to elucidate the underlying mechanism.Results It was hypothesized that the interleukin(IL)-6,tumor necrosis factor(TNF)-α,IL-1β/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/vascular endothelial growth factor(VEGF)pathway may be a key mechanism by which depressive mood promotes thyroid nodule development.In animal experiments,compared with the blank and PTU groups,the CUMS+PTU group showed significant depressive behavior,obvious thyroid enlargement and nodule formation,significantly increased thyroid volume and organ index,highly nodular hyperplasia of follicular epithelial cells,and significantly elevated protein levels of IL-1β,IL-6,TNF-α,phosphorylated(p)-JAK2/JAK2,p-STAT3/STAT3,and VEGF in thyroid tissue(P<0.05).Conclusion Depressive mood can promote the occurrence and development of thyroid nodules,potentially by increasing inflammatory factors in thyroid tissue and activating the JAK2/STAT3 signaling pathway,thereby upregulating VEGF expression.