Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.

Umbilical cord mesenchymal stem cells inhibited inflammation of bronchial epithelial cells by regulating Hedgehog pathway.

This study aimed to explore the role and mechanism of umbilical cord mesenchymal stem cells (UCMSCs) in regulating inflammation of bronchial epithelial cells. Transforming growth factor beta-1 (TGF-ß1) was used to induce inflammation in human bronchial epithelial cells. Cell proliferation was detected through CCK8 and cell apoptosis was detected by Annexin V and propidium iodide double staining. E-cadherin and α-smooth muscle actin (α-SMA) were detected by immunofluorescence, and tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in culture medium supernatant were detected by ELISA. The expression of E-cadherin, α-SMA, Sonic hedgehog (Shh), Gli1 and Snail was detected by Western blot analysis. Compared with the control group, bronchial epithelial cells treated with TGF-ß1 showed significantly decreased proliferation, increased apoptosis, increased secretion of TNF-α and IL-6, increased expression of α-SMA, Shh, Gli1 and Snail and decreased E-cadherin expression. However, co-culture with UCMSCs inhibited TGF-ß1-induced changes in human bronchial epithelial cell proliferation, apoptosis, secretion of TNF-α and IL-6 and activation of the Hedgehog pathway. In conclusion, UCMSCs have protective effects on TGF-ß1-induced inflammation in human bronchial epithelial cells by regulating the Hedgehog pathway.

BMSCs mediates endothelial cell autophagy by upregulating miR-155-5p to alleviate ventilator-induced lung injury.

In this study, we explored to detect the effects and mechanism of bone-marrow-derived mesenchymal stem cells (BMSCs) on ventilator-induced lung injury (VILI). We transplanted BMSCs in mice and then induced VILI using mechanical ventilation (MV) treatment. The pathological changes, the content of PaO2 and PaCO2 , wet/dry weight ratio (W/D) of the lung, levels of tumor necrosis factor-α and interleukin-6 in bronchoalveolar lavage fluid, and apoptosis were detected. The autophagy-associated factor p62, LC3, and Beclin-1 expression were analyzed by western blot. The quantitative polymerase chain reaction was applied to detect abnormally expressed microRNAs, including miR-155-5p. Subsequently, we overexpressed miR-155-5p in VILI mice to detect the effects of miR-155-5p on MV-induced lung injury. Then, we carried out bioinformatics analysis to verify the BMSCs-regulated miR-155-5p that target messenger RNA. It was observed that BMSCs transplantation mitigated the severity of VILI in mice. BMSCs transplantation reduced lung inflammation, strengthened the arterial oxygen partial pressure, and reduced apoptosis and the W/D of the lung. BMSCs promoted autophagy of pulmonary endothelial cells accompanied by decreased p62 and increased LC3 II/I and Beclin-1. BMSCs increased the levels of miR-155-5p in VILI mice. Overexpression of miR-155-5p alleviated lung injury in VILI mice following reduced apoptosis and increased autophagy. Finally, TAB2 was identified as a downstream target of miR-155-5p and regulated by miR-155-5p. BMSCs may protect lung tissues from MV-induced injury, inhibit lung inflammation, promote autophagy through upregulating of miR-155-5p.