International Journal of Cell Biology / 2019 / Article / Fig 7

Research Article

Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis

Figure 7

Recapitulative diagram of IL-15 pathway involved in TGF-β signaling. (a) rhIL-15 treatment counteract EMT in renal epithelial cells, preserving epithelial markers (E-cadherin and ZO-1) and inhibiting the expression of mesenchymal ones (N-cadherin, vimentin) and the production/secretion of collagen IV. (b) Dissecting the IL-15 inhibitory mechanisms reveal that the early steps of TGF-β-mediated signaling (phosphorylation and nuclear translocation of Smad2/3 complex) are not impaired by rhIL-15. However, rhIL-15 interferes on the induction of the transcription factor Snail1, a master regulator of EMT, through a long-lasting activation of c-jun pathway, consistent with the demonstrated inhibitory effect of phospho-c-jun on the formation of Smad2/3-DNA complexes.

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