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TGF-β-centered epithelial-mesenchymal transition (EMT) is a key process involved in radiation-induced pulmonary injury (RIPI) and pulmonary fibrosis. PIEZO1, a mechanosensitive calcium channel, is expressed in myeloid cell and has been found to play an important role in bleomycin-induced pulmonary fibrosis. Whether PIEZO1 is related with radiation-induced EMT remains elusive. Herein, we found that PIEZO1 is functional in rat primary type II epithelial cells and RLE-6TN cells. After irradiation, PIEZO1 expression was increased in rat lung alveolar type II epithelial cells and RLE-6TN cell line, which was accompanied with EMT changes evidenced by increased TGF-β1, N-cadherin, Vimentin, Fibronectin, and α-SMA expression and decreased E-cadherin expression. Addition of exogenous TGF-β1 further enhanced these phenomena in vitro. Knockdown of PIEZO1 partly reverses radiation-induced EMT in vitro. Mechanistically, we found that activation of PIEZO1 could upregulate TGF-β1 expression and promote EMT through Ca2+/HIF-1α signaling. Knockdown of HIF-1α partly reverses enhanced TGF-β1 expression caused by radiation. Meanwhile, the expression of PIEZO1 was up-regulated after TGF-β1 co-culture, and the mechanism could be traced to the inhibition of transcription factor C/EBPβ expression by TGF-β1. Irradiation also caused a decrease in C/EBPβ expression in RLE-6TN cells. Dual luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) confirmed that C/EBPβ represses PIEZO1 expression by binding to the PIEZO1 promoter. Furthermore, overexpression of C/EBPβ by using the synonymous mutation to C/EBPβ siRNA could reverse siRNA-induced upregulation of PIEZO1. In summary, our research suggests a critical role of PIEZO1 signaling in radiation-induced EMT by forming positive feedback with TGF-β1.

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BackgroundsSubclinical hypothyroidism (SCH) was reported to be associated with depression; however, its role in coexisting anxiety symptom in young patients with major depressive disorder (MDD) remains unclear. The objective of this study was to explore the relationship between SCH and anxiety symptom in young first-episode and drug-naïve (FEDN) MDD patients.MethodsA total of 520 outpatients diagnosed as FEDN MDD with SCH were recruited in this study. Their socio-demographic, clinical data and thyroid function parameters were collected. The Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD) were employed to measure the severity of anxiety symptom and depressive symptom, respectively. Based on the HAMA scores, patients who scored ≥ 25 were defined as anxious major depressive disorder (A-MDD) while others as non-anxious major depressive disorder (NA-MDD).ResultsThe prevalence rate of A-MDD was 15.8% in young FEDN MDD patients with comorbid SCH. Moreover, serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with A-MDD compared with those with NA-MDD (p < 0.001). Multivariate binary logistic regression analysis indicated that A-MDD was associated with serum TSH levels with an odds ratio (OR) of 1.602. Serum TSH level of 6.17 mIU/L was the critical value to distinguish A-MDD and NA-MDD, with sensitivity of 0.805 and specificity of 0.539. There were no statistically significant differences between NA-MDD and A-MDD patients in terms of socio-demographic variables, serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidases antibody (TPOAb) and anti-thyroglobulin (TgAb) levels.ConclusionsA-MDD patients presented higher serum TSH level. It is suggested that serum TSH level may be a potential biomarker for predicting moderate and severe anxiety symptoms in young FEDN MDD patients with SCH.