Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway.
Emerging evidence has exhibited an obvious decreased expression of miR-106a-5p in the ectopic endometrial tissue of endometriosis (EMS) patients. Thus far, the pathophysiological function of miR-106a-5p in EMS is unknown. A previous study showed an increased FOXC1 expression in the ectopic endometrial tissue of patients with EMS. Moreover, we found that there was a binding site of miR-106a-5p on the 3ʹUTR of FOXC1 through bioinformatics predictions. Hence, we speculated that miR-106a-5p might affect the development of EMS via targeting FOXC1. We first showed a decreased level of miR-106a-5p and an increased level of FOXC1 mRNA in ectopic endometrial tissues compared with normal tissues. Functionally, we transfected ectopic endometrial stromal cells (ESCs) with miR-106a-5p mimics or NC mimics and indicated an inhibitory role of miR-106a-5p on ESC proliferation, invasion, and migration. Mechanistically, FOXC1 was found to be a target gene of miR-106a-5p. To confirm whether miR-106a-5p exerted an inhibitory activity in ESCs via targeting FOXC1, miR-106a-5p mimic was co-transfected into ESCs with the FOXC1-plasmid or vector. We found that FOXC1 overexpression evidently reversed the results caused by a miR-106a-5p mimic in ESCs. Additionally, our results demonstrated that miR-106a-5p mimic inhibited the expression of p-Akt and p-PI3K. Collectively, these results revealed that miR-106a-5p inhibited the proliferative, migratory, and invasive ability of ESCs via directly binding to FOXC1, likely through the suppression of the PI3K and its downstream signaling pathway, which offered a potential and novel therapeutic strategy for EMS treatment.
Shi Zhaohui,Zhao Tianfeng,Wu Yongjin,Tang Zhiyuan,Wang Zaixing,Li Dingbo,Wang Chong
Allergic rhinitis (AR) is a respiratory airway disorder characterized by inflammation and barrier dysfunction. The transcription factor specificity protein 1 (SP1), a member of the Sp/Krüppel-like factor family, is known to be associated with inflammation. This study aimed to explore the impacts of SP1 on AR. An AR murine model was developed through multiple intranasal challenges with ovalbumin (OVA). Human nasal epithelial cells (HNEpCs) were cultured at the air–liquid interface (ALI) and treated with IL-13 to create a cell model with barrier damage. Bioinformation samples revealed that SP1 expression was upregulated in nasal epithelial cells of people with AR. High Sp1 expression was observed in AR mice nasal mucosa. Silencing Sp1 reduced nasal rubbing, sneezing, serum levels of IgE, histamine, and nasal swelling in AR mice. Additionally, Sp1 silencing inhibited goblet cell proliferation, eosinophilic infiltration, and levels of IL-4 and IL-13. Sp1 knockdown reversed the elevated fluorescein isothiocyanate–dextran 4 kDa permeability, nasal epithelial cell shedding, and decreased expression of E-cadherin and Claudin-1. In vitro, knocking down SP1 led to an increase in transepithelial electrical resistance and levels of E-cadherin and Claudin-1. Mechanistically, SP1 upregulated forkhead box C1 (FOXC1) expression through transcriptional activity, and FOXC1 overexpression reversed the protective effects of SP1 silencing on epithelial barrier damage. Overall, our findings suggest that SP1 aggravates AR, potentially through the transcriptional activation of SP1 to FOXC1.
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