Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES‐associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP.Methods: Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ‐binding transcriptional co‐activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens‐1 (ZO‐1), E‐cadherin, and transforming growth factor‐beta1 (TGF‐β1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO‐1, E‐cadherin, TGF‐β1, and Smad7 were measured by Western blot.Results: Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF‐β1, ZO‐1, and E‐cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO‐1, E‐cadherin, and TGF‐β1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells.Conclusions: Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF‐β1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

Backgrounds: Obstructive sleep apnea (OSA) and hypertension both had significant impacts on human health. Whether OSA increases the risk of hypertension in relation to heredity remains unclear. We sought to clarify this issue using bidirectional Mendelian randomization (MR) analysis in large cohorts. Methods: A bidirectional two‐sample MR was conducted to evaluate the potential causality between OSA and hypertension by selecting single‐nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from meta genome‐wide association studies (mGWAS). The inverse‐variance weighted (IVW) method was the main approach for data analysis to estimate the possible causal effects. Alternative methods such as MR‐Egger, the MR pleiotropy residual sum and outlier (MR‐PRESSO), and leave‐one‐out analysis methods were also performed as sensitivity analysis approaches. In order to adjust the confounding factors, a multivariable MR (MVMR) was also performed. Results: In the forward analysis, the IVW analysis demonstrated a significant association of OSA on increased hypertension risk (OR, 1.044; 95% CI, 1.012–1.076; and p = 0.006), DBP value (β, 0.041; 95% CI, 0.012–0.071; and p = 0.005), and hypertension of siblings risk (OR, 1.025; 95% CI, 1.003–1.049; and p = 0.028), but after adjusting the confounding factors (BMI, smoking, and alcohol consumption), the association disappeared. The reverse analysis demonstrated the causal effect of hypertension of father on elevated OSA risk (OR, 3.803; 95% CI, 1.135–12.726; and p = 0.030). Conclusions: Our forward analysis found the association between OSA and increased hypertension risk, DBP, and hypertension risk of siblings, but after adjusting the confounding factors, the association disappeared; on the reverse analysis, we found the causal effect of hypertension of father on elevated OSA risk.

Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Early Nasal polyps’ formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps’ development is regulated by TGF-β1-mediated PAI-1 reduction. 3b.