Fig. 5: MSCs secrete kynurenine (Kyn) to activate AMPK pathway. | Cell Death & Disease

Fig. 5: MSCs secrete kynurenine (Kyn) to activate AMPK pathway.

From: Mesenchymal stem cells in tumor microenvironment: drivers of bladder cancer progression through mitochondrial dynamics and energy production

Fig. 5

Metabolic pathway and enrichment analysis using MetaboAnalyst(a). The concentrations of Kyn in MSC-CM were higher than those in the control medium (b). CCK8 assays and wound healing assays revealed that Kyn promoted UMUC-3 cell proliferation and migration (c, n). Immunoblot showed that the expression of PKA, LKB1, p-AMPK, PINK1, PARK2, PGC1α, NRF1, TFAM, DRP1, and MFN2 in UMUC-3 was increased after treatment with increasing concentrations of Kyn (d). AMPK inhibitor (AMPKi) dorsomorphin effectively inhibited the AMPK pathway, thereby attenuating the activating effect of Kyn on AMPK (e). Immunoblot showed that the expression-promoting effect of Kyn to PGC1α, NRF1, TFAM, DRP1, and MFN2 was prevented by the inhibition of AMPK (f). Kyn induced MMP hyperpolarization, enhanced mitochondrial morphology, and increase mitochondrial numbers, all of which were impeded by AMPKi (g, h). Mitostress assay demonstrated that Kyn significantly promoted mitochondrial metabolism (i), including a significant increase in basal cellular OCR (j), ATP production (k), and maximum respiration (l) in UMUC-3 cells compared to the control. CCK8 and wound closure assays showed that AMPKi could disrupt the pro-tumor effect of Kyn (m, n). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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