Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells

Figure 1 Implication of miR-21-5p and miR-214-5p in regulation of signal transducer and activator of transcription 3 signaling pathway. A: Normal endometrial epithelial cells produce a high amount of exosomes enriched in miR-12-5p and miR-214-5p, followed by adaptation by mesenchymal stromal cells (MSCs). MiR-21-5p and miR-214-5p then stably connect with the 3’-untranslated region of signal transducer and activator of transcription 3 (STAT3), inducing the mRNA degradation. This event is directly associated with the total absence or low expression of STAT3, blocking MSC migration and differentiation; B: Hypoxic damaged-endometrial epithelial cells are responsible for exosome production with low content of miR-21-5p and miR-214-5p. The absence of the aforementioned miRNAs induces proper mRNA transcription and STAT3 production. Eventually, p-STAT3 is translocated to the MSC nucleus, thus enhancing the migratory and differentiation capacity of the cells. EEC: Endometrial epithelial cell; MSC: Mesenchymal stromal cell; STAT3: Signal transducer and activator of transcription 3.