MiR-216a-3p promotes differentiation of BMMSCs into ACE II cells via Wnt/β-catenin pathway

OBJECTIVE: To explore whether miR-216a-3p could promote differentiation of bone marrow mesenchymal stem cells (BMMSCs) into type II alveolar epithelial cells (ACE II) via Wnt/β-catenin pathway, thereby alleviating neonatal respiratory distress syndrome (NRDS).

MATERIALS AND METHODS: BMMSCs were directionally differentiated into ACE II cells. Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were detected at the different time points after cell differentiation. Enzyme-linked immunosorbent assay (ELISA) was applied to detect inflammatory factors in the culture medium, including interleukin-1 (IL-1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and Interferon-α (INF-α). After overexpression or knockdown of miR-216a-3p in BMMSCs, expressions of ACE II cell-specific transcription factors and inflammatory factors were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Rescue experiments were carried out after DKK-1 treatment in BMMSCs.

RESULTS: Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were elevated with the prolongation of cell differentiation. Overexpression of miR-216a-3p elevated levels of pro-inflammatory factors (IL-1, TNF-α, and INF-α) and reduced anti-inflammatory factor (IL-10). Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were remarkably increased at 7 d and 14 d compared to those detected at 1 d. Overexpression of miR-216a-3p in BMMSCs downregulated Wnt3a expression. The regulatory effect of miR-216a-3p on BMMSCs differentiation was partially reversed by DKK-1 treatment.

CONCLUSIONS: Knockdown of miR-216a-3p induces differentiation of BMMSCs into ACE II cells through Wnt/β-catenin pathway, thereby alleviating NRDS.

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