RESUMO
BACKGROUND: Nasal polyposis is a multi-factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. OBJECTIVE: The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)-ß1-induced myofibroblast differentiation and ECM accumulation in nasal polyp-derived fibroblasts (NPDFs). METHODS: Nasal polyp-derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF-ß1-induced NPDFs. Expression levels of HDAC2, α-smooth muscle actin (SMA), TGF-ß1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT-PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT-PCR and western blot. The epigenetic effect on α-SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67-positive cell staining and cytotoxicity was assessed by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: The expression levels of HDAC2, α-SMA and TGF-ß1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α-SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α-SMA gene promoter in TGF-ß1-induced NPDFs. TSA inhibited TGF-ß1-induced Smad 2/3 and rescued TGF-ß1-suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF-ß1-induced NPDFs and has no cytotoxic effect in NPDFs. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.
Assuntos
Diferenciação Celular , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , Acetilação/efeitos dos fármacos , Actinas/genética , Actinas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Epigênese Genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 2/antagonistas & inibidores , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Fosforilação/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Thyroid hemiagenesis is a rare abnormality in which one thyroid lobe fails to develop. Most of the patients diagnosed have an associated thyroid disease. We report the case of a 32-year-old woman who presented with a left thyroid mass which had been gradually increasing in size over a period of two years. A thyroid scan revealed the absence of the right thyroid lobe and isthmus, and a hypoactive nodule was evident in the lower pole of the left lobe. Ultrasonography confirmed the right lobe and the isthmus agenesis. The operative findings confirmed hemiagenesis of the right lobe and nodular hyperplasia in the left lobe. The purpose of this report is to present a patient with hemiagenesis of the thyroid gland who concomitantly had nodular hyperplasia; we also stress the importance of pre-operative differentiation between benign lesions and malignancy in order to aid critical decision making and to facilitate preservation of thyroid function if possible.
