Abstract
Background:
Mesenchymal stem cells (MSCs) isolated from umbilical cord blood (UCB) exhibit significant therapeutic efficacy in endometriosis; however, the molecular mechanisms governing their regulation remain incompletely elucidated. This study delves into the regulatory functions of miR-210-3p and miR-31-5p, which are secreted via exosomes from hypoxia-damaged endometrial epithelial cells, in modulating the behavior of UCB-MSCs.
Methods:
UCB-MSCs were transfected with specific inhibitors targeting miR-210-3p and miR-31-5p. Proliferation and migratory capacities were quantified using CCK8, EdU incorporation, Transwell, and scratch wound healing assays. Western blotting was employed to assess the expression of endometrial epithelial markers (CD9 and CK19) and stromal markers (Vimentin and CD13), alongside the phosphorylation status of JAK2 and STAT3. Dual-luciferase reporter assays were conducted to validate SDF2 and FGF7 as direct targets of miR-210-3p and miR-31-5p, respectively.
Results:
Suppression of miR-210-3p and miR-31-5p significantly augmented the proliferative and migratory abilities of UCB-MSCs, while simultaneously enhancing their differentiation into endometrial epithelial cells and attenuating their transition into stromal cells. Concurrently, the phosphorylation levels of JAK2 and STAT3 were markedly elevated. Overexpression of SDF2 and FGF7 further amplified the proliferative, migratory, and epithelial differentiation capacities of UCB-MSCs, accompanied by heightened activation of the JAK2/STAT3 signaling pathway. Notably, SDF2 overexpression and FGF7 overexpression effectively counteracted the inhibitory effects exerted by miR-210-3p and miR-31-5p mimics on UCB-MSC proliferation, migration, and epithelial differentiation, mediated through the modulation of JAK2/STAT3 signaling.
Conclusion:
miR-210-3p and miR-31-5p orchestrate the functional dynamics of UCB-MSCs by targeting SDF2 and FGF7, respectively, through the JAK2/STAT3 pathway. These findings unveil novel mechanistic insights into the regenerative potential of UCB-MSCs, offering promising avenues for therapeutic advancements in endometriosis.
Supplementary Information:
The online version contains supplementary material available at 10.1186/s13287-025-04621-x.
Keywords:
Differentiation; FGF7; JAK2/STAT3; Migration; Proliferation; SDF2; Umbilical cord blood mesenchymal stem cells; miR-210-3p; miR-31-5p.