Translational research : the journal of laboratory and clinical medicine
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Dysregulation of type II alveolar epithelial cells (AECII) plays a vital role in the initiation and development of pulmonary fibrosis (PF). Dachshund homolog 1 (Dach1), frequently expressed in epithelial cells with stem cell potential, controls cell proliferation, apoptosis, and cell cycle in tissue development and disease process. In this study, we demonstrated that the lungs collected from PF patients and mice of Bleomycin (BLM)-treated were characterized by low expression of Dachshund homolog 1 (Dach1), especially in AECII. ⋯ Conversely, primary AECII with Dach1 depletion were more susceptible to apoptosis in vivo. Mechanically, Dach1 combined with C-Jun protooncogene selectively bound to the promoter of B-cell lymphoma 2 interacting mediators of cell death (Bim), by which it repressed Bim expression and alleviated epithelial apoptosis. Taken together, our data support that Dach1 in AECII contributes to the progression of PF and may be a viable target for the prevention and treatment of PF.
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According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. ⋯ Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.