High salt stress in kidney tube cells may trigger self-cleaning processes in nearby support cells through released glutamate

Epithelial hyperosmotic stress increases extracellular glutamate levels, which may activate autophagy in neighboring fibroblasts.

• Hyperosmotic stress in tubular epithelial cells triggers significant nuclear translocation of transcription factor EB (TFEB) in fibroblasts.
• Fibroblasts respond to epithelial-derived signals by increasing the expression of genes related to lysosomal activity and autophagy.
• Changes in amino acid transporter gene expression were noted in epithelial cells under hyperosmotic stress.
• Conditioned media analysis showed elevated extracellular glutamate levels following hyperosmotic stress.
• Glutamate alone was capable of inducing TFEB nuclear translocation and activating autophagy in fibroblasts.
• Both the co-culture of epithelial cells under hyperosmotic stress and glutamate treatment activated AMP-activated protein kinase, inhibiting mTORC1 signaling, which supports TFEB activation.

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