YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome - 03/02/23
Abstract |
Acute respiratory distress syndrome (ARDS) contributes to higher mortality worldwide. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have immunomodulatory and regenerative potential. However, the effects of hUC-MSCs as an ARDS treatment remain unclear. We investigated the role of hUC-MSCs in the differentiation of type II alveolar epithelial cells (AECII) by regulating Yes-associated protein (YAP) in ARDS. Male C57BL/6JNarl mice were intratracheally (i.t.) administered lipopolysaccharide (LPS) to induce an ARDS model, followed by a single intravenous (i.v.) dose of hUC-MSCs. hUC-MSCs improved pulmonary function, decreased inflammation on day 3, and mitigated lung injury by reducing the lung injury score and increasing lung aeration (%) in mice on day 7 (p < 0.05). hUC-MSCs inactivated YAP on AECII and facilitated cell differentiation by decreasing Pro-surfactant protein C (Pro-SPC) and galectin 3 (LGALS3) while increasing podoplanin (T1α) in lungs of mice (p < 0.05). In AECII MLE-12 cells, both coculture with hUC-MSCs after LPS exposure and the YAP inhibitor, verteporfin, reduced Pro-SPC and LGALS3, whereas the YAP inhibitor increased T1α expression (p < 0.05). In conclusion, hUC-MSCs ameliorated lung injury of ARDS and regulated YAP to facilitate AECII differentiation.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | hUC-MSCs reduced lung injury and inflammation in mice with LPS-induced ARDS. |
• | Dynamic YAP regulation on AECII was mediated by hUC-MSCs in LPS-induced ARDS. |
• | Inactivation of YAP facilitated LPS-induced AECII differentiation in response to hUC-MSCs. |
• | hUC-MSCs may have potential in the treatment of ARDS. |
Abbreviations : AECI, AECII, ANOVA, ARDS, BALF, BW, CBA, CD, CLDN4, COPD, DAPI, EF50, ELISA, hUC-MSCs, IL, KC, LGALS3, LPS, micro-CT, MSCs, PATS, PBS, PEF, Pro-SPC, pYAP, SEM, SpO2, TNF-α, YAP
Keywords : Alveoli, Inflammation, Pneumocytes, Regeneration, Stem cells
Plan
Vol 159
Article 114302- mars 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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