Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tomoya Suehiro, Khoja Mouhand Ahmad, Nguyen Truong Duc Hoang, Bingwen Xu, Honoka Komatsu, Komei Kurachi, Hiroki Nikawa, Yuichi Mine, Tohru Matsuki, Katsura Asano, Makiko Fujii
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引用次数: 0

Abstract

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

激活血小板衍生生长因子受体可通过 AKT 途径调节恶性间皮瘤细胞中的结缔组织生长因子蛋白水平。
恶性间皮瘤(MM)是一种与难治性石棉暴露有关的疾病,其发病率在全球范围内持续上升,并且在很大程度上对各种治疗方法具有抗药性。我们之前的研究发现,结缔组织生长因子(CTGF)蛋白的表达与间皮瘤的恶性程度密切相关,这凸显了了解间皮瘤细胞中 CTGF 调控的重要性。在这项研究中,我们首次证明了血小板衍生生长因子受体(PDGFR)配体 PDGF-BB 的刺激会增加 CTGF 蛋白表达水平,而不会影响 CTGF mRNA 水平。抑制 PDGFR 会导致 CTGF 蛋白表达的减少,这表明 PDGFR 的活化对调节 MM 细胞中 CTGF 蛋白的表达至关重要。PDGF-BB 还激活了蛋白激酶 B(AKT)通路,抑制 AKT 磷酸化可抑制 PDGFR 诱导的 CTGF 蛋白表达,这表明 PDGFR 通过 AKT 通路作用于 CTGF 的上游。这加强了 CTGF 蛋白作为 MM 恶性肿瘤关键调控因子的作用。此外,PDGFR 的激活导致了 AKT 下游蛋白质合成的关键调节因子 mTOR 和 4E-BP1 的磷酸化,这表明 PDGFR 通过调节 CTGF mRNA 翻译来控制 CTGF 蛋白的表达。
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
Journal of biochemistry
Journal of biochemistry 生物-生化与分子生物学
CiteScore
4.80
自引率
3.70%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.
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