Tabandeh Mohammad Reza, Soroush Fatemeh, Dayer Dian
Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Cellular and Molecular Research Center, Medical Basic Sciences Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cell J. 2022 Oct 1;24(10):586-595. doi: 10.22074/cellj.2022.8320.
Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation ability and viability of stem cells, but little is known about the critical function of Itaconate on the stem cell fate. The objective of the present study was to determine the regulatory effects of Itaconic acid on the cell viability and transcription of apoptosis and autophagy pathways genes in the rat adipose derived mesenchymal stem cells (ADMSCs).
In this experimental study, the ADMSCs were incubated with 125 μM and 250 μM dimethyl itaconate (DMI) for 24 hours or 48 hours. The expression of apoptosis pathway genes ( and ) and autophagy pathway genes ( and ) were determined using real time polymerase chain reaction (PCR) assay. Using the ELISA method, cellular level of phospho-NRF2 protein was measured.
The results indicated that DMI increased the expression of NRF2 protein, altered the expression of some apoptosis genes ( and ), and changed the expression of some autophagy related genes ( and ) in ADMSCs. DMI had no obvious effect on the transcription of caspases enzymes.
Because autophagy activation and apoptosis suppression can protect stem cells against environmental stress, it seems Itaconate can affect the functions and viability of ADMSCs via converse regulation of these pathways.
衣康酸是一种新型的调节性免疫代谢物，由炎性巨噬细胞合成。它作为一种抗炎介质，调节多种代谢和信号通路，特别是Nrf2通路。免疫代谢物可以影响干细胞的干性、分化能力和活力，但关于衣康酸对干细胞命运的关键作用知之甚少。本研究的目的是确定衣康酸对大鼠脂肪来源间充质干细胞（ADMSCs）细胞活力以及凋亡和自噬通路相关基因转录的调节作用。
在本实验研究中，将ADMSCs与125μM和250μM的衣康酸二甲酯（DMI）孵育24小时或48小时。使用实时聚合酶链反应（PCR）测定法确定凋亡通路基因（ 和 ）和自噬通路基因（ 和 ）的表达。采用酶联免疫吸附测定（ELISA）法测量磷酸化NRF2蛋白的细胞水平。
结果表明，DMI增加了ADMSCs中NRF2蛋白的表达，改变了一些凋亡基因（ 和 ）的表达，并改变了一些自噬相关基因（ 和 ）的表达。DMI对半胱天冬酶的转录没有明显影响。
由于自噬激活和凋亡抑制可以保护干细胞免受环境应激，衣康酸似乎可以通过对这些通路的反向调节来影响ADMSCs的功能和活力。
