Browsing by Author "Wang, Yue"

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    Identification of multiple isoforms of glucocorticoid receptor in nasal polyps of patients with chronic rhinosinusitis
    (2022-06-11) Shao, Shan; Wang, Yue; Zhao, Yan; Xu, Yuan; Wang, Tie; Du, Kun; Bao, Shiping; Wang, Xiangdong; Zhang, Luo
    Abstract Background The conventional belief that glucocorticosteroid (GC) acts through a single brand glucocorticoid receptor (GR)α protein has changed dramatically with the discovery of multiple GR isoforms. We aimed to evaluate whether multiple GR protein isoforms are expressed in chronic rhinosinusitis with nasal polyps (CRSwNP) and whether GR protein isoform expression profiles differ between different endotypes of CRSwNP. Methods Thirty-eight patients with CRSwNP and ten healthy volunteers were included. The protein expression of multiple GR isoforms in nasal polyps (NPs) tissue and control mucosae was examined by western blot analysis with different GR antibodies. Results Five bands, including three bands for known proteins (GRα-A/B, GRα-C, and GRα-D) and two bands for unidentified proteins at 67 kilodaltons (kDa) and 60 kDa, were identified with both total GR antibody (PA1-511A) and GRα-specific antibody (PA1-516). GRα-D intensity, which was abundant in nasal mucosa, was significantly increased in the CRSwNP group and was especially elevated in the noneosinophilic CRSwNP (NE-CRSwNP) group (PA1-511A: P < 0.001 and P = 0.0018; PA1-516: P < 0.003 and P = 0.006, respectively). Additionally, the intensities of the newly recognized 67 kDa and 60 kDa bands were much greater in the NE-CRSwNP subgroup than in the eosinophilic CRSwNP (E-CRSwNP) subgroup; in the E-CRSwNP subgroup, the median intensities were even lower than those in the control group. Conclusions This study provides evidence that nasal tissues express multiple GR protein isoforms. GR protein isoforms presented disease and tissue-specific expression profiles that differed between the CRSwNP and control groups and between the E-CRSwNP and NE-CRSwNP subgroups. Graphical abstract
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    MicroRNA miR-223 modulates NLRP3 and Keap1, mitigating lipopolysaccharide-induced inflammation and oxidative stress in bovine mammary epithelial cells and murine mammary glands
    (2023-09-14) Zhou, Man; Barkema, Herman W.; Gao, Jian; Yang, Jingyue; Wang, Yue; Kastelic, John P.; Khan, Sohrab; Liu, Gang; Han, Bo
    Abstract Bovine mastitis, the most prevalent and costly disease in dairy cows worldwide, decreases milk quality and quantity, and increases cow culling. However, involvement of microRNAs (miRNAs) in mastitis is not well characterized. The objective was to determine the role of microRNA-223 (miR-223) in regulation of the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and kelch like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) oxidative stress pathway in mastitis models induced by lipopolysaccharide (LPS) treatment of immortalized bovine mammary epithelial cells (bMECs) and murine mammary glands. In bMECs cultured in vitro, LPS-induced inflammation downregulated bta-miR-223; the latter interacted directly with the 3’ untranslated region (3’ UTR) of NLRP3 and Keap1. Overexpression of bta-miR-223 in bMECs decreased LPS and Adenosine 5’-triphosphate (ATP)-induced NLRP3 and its mediation of caspase 1 and IL-1β, and inhibited LPS-induced Keap1 and Nrf2 mediated oxidative stress, whereas inhibition of bta-miR-223 had opposite effects. In an in vivo murine model of LPS-induced mastitis, increased miR-223 mitigated pathology in the murine mammary gland, whereas decreased miR-223 increased inflammatory changes and oxidative stress. In conclusion, bta-miR-223 mitigated inflammation and oxidative injury by downregulating the NLRP3 inflammasome and Keap1/Nrf2 signaling pathway. This study implicated bta-miR-223 in regulation of inflammatory responses, with potential as a novel target for treating bovine mastitis and other diseases.