title: Mechanisms and kinetics of proliferation and fibrosis development in a mouse model of thyrocyte hyperplasia.
abstract: IFN-γ(-/-) NOD.H-2h4 mice develop autoimmune disease with extensive hyperplasia and proliferation of thyroid epithelial cells (TEC H/P) and fibrosis. Splenic T cells from donors with severe TEC H/P transfer TEC H/P to SCID recipients. The goal of this study was to determine what factors control TEC H/P development/progression by examining T cells, markers of apoptosis, senescence and proliferation in thyroids of SCID recipients over time. At 28days, T cell infiltration was maximal, thyrocytes were proliferating, and fibrosis was moderate. At days 60 and 90, thyroids were larger with more fibrosis. T cells, cytokines and thyrocyte proliferation decreased, and cell cycle inhibitor proteins, and anti-apoptotic molecules increased. T cells and thyrocytes had foci of phosphorylated histone protein H2A.X, indicative of cellular senescence, when TEC H/P progressed and thyrocyte proliferation declined. Some thyrocytes were regenerating at day 90, with irregularly shaped empty follicles and ciliated epithelium. Proliferating thyrocytes were thyroid transcription factor (TTF1)-positive, suggesting they derived from epithelial cells and not brachial cleft remnants.
authors.affiliation: Department of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Radu Tudor
authors.initials: RT
authors.lastname: Ciornei
authors.affiliation: Department of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Surgery, University of Missouri, Columbia, MO 65212, United States; Department of Microbiology, Immunology and Pathology, Des Moines University, Des Moines, IA 50312, United States.
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Surgery, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Medicine, University of Missouri, Columbia, MO 65212, United States; Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO 65212, United States. Electronic address: mullenh@health.missouri.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*; D000072637:Thyroid Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D013961:Thyroid Gland / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D006657:Histones; D007371:Interferon-gamma; D014157:Transcription Factors; C504004:Ttf1 protein, mouse; C475961:gamma-H2AX protein, mouse
keywords: Autoimmunity; Fibrosis; Senescence; Thyrocyte proliferation; Thyroid epithelial cell (thyrocyte) hyperplasia