Int J Med Sci 2019; 16(12):1631-1641. doi:10.7150/ijms.35936 This issue Cite

Research Paper

Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1

Pingli Yang1,3, Shan Chen1, Gang Zhong1, Weijia Kong1,2✉, Yanjun Wang1✉

1. Department of otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
2. Institutes of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
3. Department of otorhinolaryngology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, 832000, China

Citation:
Yang P, Chen S, Zhong G, Kong W, Wang Y. Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1. Int J Med Sci 2019; 16(12):1631-1641. doi:10.7150/ijms.35936. https://www.medsci.org/v16p1631.htm
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Abstract

Epithelial-mesenchymal transition (EMT) has been reported to occur in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Among the cytokines that cause EMT, high mobility group box 1 (HMGB1) has been shown to give rise to EMT in airway epithelial cells. However, the mechanism of HMGB1-induced EMT in ECRSwNP is unknown. We explored the mechanism and possible inhibitor. Immunohistochemistry (IHC), immunofluorescence (IF), and western blot assay were used to detect the expression and location of HMGB1, peroxisome proliferator-activated receptor-γ (PPAR-γ), and EMT markers in eighteen ECRSwNP and twelve normal nasal mucosa tissues. Epithelial cells isolated from ECRSwNP were cultured with various doses of recombinant human HMGB1 (rhHMGB1) to study the expression of PPAR-γ, and EMT markers. Additionally, the ligand of PPAR-γ was incubated with epithelial cells to interfere with the effects of lipopolysaccharide (LPS) or rhHMGB1 to explore the effect on expression of HMGB1 and EMT markers. These results suggest that HMGB1 was highly expressed in ECRSwNP compared with its expression in control tissues, and EMT was also found highly in ECRSwNP compared with control tissues. Moreover, the cytoplasmic accumulation of HMGB1 in ECRSwNP was obvious compared with normal tissues. We also found dose-dependent induction by rhHMGB1 of up-regulation of N-cadherin and vimentin and down-regulation of ZO-1 and E-cadherin in epithelial cells isolated from ECRSwNP. The agonist of PPAR-γ not only reduced release of HMGB1 induced by LPS, but also reversed the EMT. The protective role of PPAR-γ also appeared in cells that had been incubated with rhHMGB1. In the current study, we discovered that the agonist of PPAR-γ has a potential role in inhibited HMGB1-induced EMT in ECRSwNP. The agonist of PPAR-γ may contribute to inhabit epithelial cells to become mesenchymal-like cells which play an important role in the pathogenesis of ECRSwNP.

Keywords: Epithelial-mesenchymal transition, chronic rhinosinusitis with nasal polyps, high mobility group box 1, peroxisome proliferator-activated receptor-γ


Citation styles

APA
Yang, P., Chen, S., Zhong, G., Kong, W., Wang, Y. (2019). Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1. International Journal of Medical Sciences, 16(12), 1631-1641. https://doi.org/10.7150/ijms.35936.

ACS
Yang, P.; Chen, S.; Zhong, G.; Kong, W.; Wang, Y. Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1. Int. J. Med. Sci. 2019, 16 (12), 1631-1641. DOI: 10.7150/ijms.35936.

NLM
Yang P, Chen S, Zhong G, Kong W, Wang Y. Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1. Int J Med Sci 2019; 16(12):1631-1641. doi:10.7150/ijms.35936. https://www.medsci.org/v16p1631.htm

CSE
Yang P, Chen S, Zhong G, Kong W, Wang Y. 2019. Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1. Int J Med Sci. 16(12):1631-1641.

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