Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 building, 50-375, Wroclaw, Poland.
International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
Cell Commun Signal. 2021 Nov 3;19(1):106. doi: 10.1186/s12964-021-00772-5.
Protein tyrosine phosphatase 1B (PTP1B) and low molecular weight protein tyrosine phosphatase (LMPTP) are implicated in the development of metabolic disorders. Yet, their role in progenitor stem cell adipogenic differentiation and modulation of mitochondrial dynamics remains elusive.
In this study, we decided to investigate whether inhibition of PTP1B and LMPTP enhance adipogenic differentiation of metabolically impaired progenitor stem cells via modulation of mitochondrial bioenergetics and dynamics. Cells were cultured under adipogenic conditions in the presence of PTP1B and LMPTP inhibitors, and were subjected to the analysis of the main adipogenic-related and mitochondrial-related genes using RT-qPCR. Protein levels were established with western blot while mitochondrial morphology with MicroP software.
Selective inhibitors of both PTP1B and MPTP enhanced adipogenic differentiation of metabolically impaired progenitor stem cells. We have observed enhanced expression of PPARy and adiponectin in treated cells. What is more, increased antioxidative defence and alternations in mitochondrial bioenergetics were observed. We have found that inhibition of PTP1B as well as C23 activates oxidative phosphorylation and enhances mitochondrial fusion contributing to enhanced adipogenesis.
The presented data provides evidence that the application of PTP1B and LMPTP inhibitors enhances adipogenesis through the modulation of mitochondrial dynamics. Video abstract.
蛋白酪氨酸磷酸酶 1B（PTP1B）和低分子量蛋白酪氨酸磷酸酶（LMPTP）与代谢紊乱的发展有关。然而，它们在祖细胞干细胞成脂分化和调节线粒体动力学中的作用仍不清楚。
在这项研究中，我们决定研究抑制 PTP1B 和 LMPTP 是否通过调节线粒体生物能学和动力学来增强代谢受损祖细胞干细胞的成脂分化。细胞在成脂条件下培养，存在 PTP1B 和 LMPTP 抑制剂，并使用 RT-qPCR 分析主要的成脂相关和线粒体相关基因。用 Western blot 确定蛋白水平，用 MicroP 软件确定线粒体形态。
两种 PTP1B 和 MPTP 的选择性抑制剂均增强了代谢受损祖细胞干细胞的成脂分化。我们观察到处理细胞中 PPARγ和脂联素的表达增强。此外，还观察到抗氧化防御的增加和线粒体生物能的改变。我们发现抑制 PTP1B 以及 C23 激活氧化磷酸化并增强线粒体融合，有助于增强成脂分化。
所提供的证据表明，应用 PTP1B 和 LMPTP 抑制剂通过调节线粒体动力学增强成脂分化。视频摘要。
