Ligand-Activated Peroxisome Proliferator-Activated Receptor β/δ Facilitates Cell Proliferation in Human Cholesteatoma Keratinocytes.

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

PPAR Research Pub Date : 2020-12-22 eCollection Date: 2020-01-01 DOI:10.1155/2020/8864813

Chen Zhang, Yang-Wenyi Liu, Zhangcai Chi, Bing Chen

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引用次数: 3

Abstract

Cholesteatoma is characterized by both the overgrowth of hyperkeratinized squamous epithelium and bone erosion. However, the exact mechanism underlying the hyperproliferative ability of cholesteatoma remains unknown. In this study, we investigated PPAR β/δ expression in human surgical specimens of cholesteatoma and analyzed its functional role as a regulator of epithelial keratinocyte hyperproliferation. We found that the expression of PPAR β/δ was significantly upregulated in cholesteatoma and ligand-activated PPAR β/δ markedly promoted the proliferation of cholesteatoma keratinocytes. Furthermore, we showed that PPAR β/δ activation increased PDK1 expression and decreased PTEN generation, which led to increased phosphorylation of AKT and GSK3β and increased the expression level of Cyclin D1. Overall, our data suggested that the proliferating effect of PPAR β/δ on the cholesteatoma keratinocytes was mediated by the positive regulation of the PDK1/PTEN/AKT/GSK3β/Cyclin D1 pathway. These findings warranted further investigation of PPAR β/δ as a therapeutic target for recurrent or residual cholesteatoma.

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配体活化过氧化物酶体增殖物活化受体β/δ促进人胆脂瘤角质形成细胞的增殖。

胆脂瘤的特征是角化过度的鳞状上皮过度生长和骨侵蚀。然而，胆脂瘤高增殖能力的确切机制尚不清楚。在这项研究中，我们研究了PPAR β/δ在人胆脂瘤手术标本中的表达，并分析了其作为上皮角质细胞过度增殖的调节因子的功能作用。我们发现PPAR β/δ在胆脂瘤中的表达显著上调，配体激活的PPAR β/δ显著促进了胆脂瘤角质形成细胞的增殖。此外，我们发现PPAR β/δ激活增加了PDK1的表达，减少了PTEN的产生，从而导致AKT和GSK3β磷酸化增加，Cyclin D1表达水平升高。总之，我们的数据表明PPAR β/δ对胆脂瘤角质形成细胞的增殖作用是通过PDK1/PTEN/AKT/GSK3β/Cyclin D1通路的正调控介导的。这些发现为进一步研究PPAR β/δ作为复发性或残留胆脂瘤的治疗靶点提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.