RESUMO
TGF-ß, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-ß/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-ß, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.
Assuntos
Cirrose Hepática/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Tri-Iodotironina/metabolismo , Animais , Bleomicina/efeitos adversos , Bleomicina/farmacologia , Intoxicação por Tetracloreto de Carbono/genética , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos , Camundongos Knockout , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta/genética , Tri-Iodotironina/genéticaRESUMO
Intervention programs based on self-compassion have demonstrated their efficacy both in reducing psychological distress and increasing well-being. The goal of this study was to test the efficacy of an online intervention to increase mindfulness and self-compassion levels in a non-clinical sample in a highly stressful context: the ten weeks of lockdown imposed in the early stages of the COVID-19 pandemic. The intervention sessions consisted of thirty-minute guided meditations followed by thirty minutes of inquiry. Sixty-one participants completed two thirds of the sessions or more, and 65 individuals participated in a waiting-list (WL) control group. Self-compassion, anxiety, depression and stress levels were assessed. The analysis of pre-post results suggests that the interventions increased self-compassion levels and decreased anxiety, depression and stress levels, whereas the WL group did not show any significant changes. The emotional changes in the intervention group were associated with the increase in self-compassion. However, at follow-up, the scores of emotional distress variables returned to the initial pre-intervention scores. These data can be interpreted in line with previous results that have shown the efficacy of self-compassion-based intervention programs. Given that this efficacy was not maintained at follow-up, data are discussed according to the pervasive role of a highly stressful context and-as described in other studies-the need for regular practice to maintain the benefits obtained.