Itaconic Acid; as A Novel Immunometabolite, DifferentiallyRegulates The Transcription of Autophagy AssociatedGenes in Rat Adipose Mesenchymal S tem Cells

Objective: Itaconate is a novel regulatory immunometabolitethat is synthesized by inflammatory macrophages and acts as ananti-inflammatory mediator by regulation of several metabolicand signaling pathways, in particular, the Nrf۲ pathway. Theimmunometabolites can affect the s temness potency, differentiationability, and viability of s tem cells, but little is knownabout the critical function of itaconate on s tem cell fate. In thepresent s tudy, the effect of itaconate on viability and transcriptionof autophagy-related genes in rat adipose-derived mesenchymals tem cells (ADMSCs) was inves tigated.Materials and Methods: In this experimental s tudy, the ADMSCswere incubated with ۱۲۵ μM and ۲۵۰ μM dimethyl itaconate(DMI) for ۲۴ hours or ۴۸ hours. The expression of genesassociated with autophagy (Atg۱۲, Atg۵, Beclin, LC۳B, andP۶۲) pathways was determined using quantitative polymerasechain reaction (qPCR) assay. The cellular level of phospho-Nrf۲ protein was measured using the ELISA method.Results: The results indicated that DMI increased the expressionof Nrf۲ protein and changed the expression of some autophagy-related genes (LC۳B, Becline, and P۶۲) in ADMSCs.Conclusion: Because autophagy activation can protect s temcells under environmental s tress, it is possible that itaconate,by converse regulation of the autophagy pathway, can affect thefunctions and viability of ADMSCs.

کلیدواژه ها:

Autophagy ، Itaconic Acid ، Rat Adipose MesenchymalS tem Cells