PMID- 36701989 OWN - NLM STAT- MEDLINE DCOM- 20230210 LR - 20230210 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 159 DP - 2023 Mar TI - YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome. PG - 114302 LID - S0753-3322(23)00090-2 [pii] LID - 10.1016/j.biopha.2023.114302 [doi] AB - 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 (T1alpha) 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 T1alpha expression (p < 0.05). In conclusion, hUC-MSCs ameliorated lung injury of ARDS and regulated YAP to facilitate AECII differentiation. CI - Copyright (c) 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Chen, Xiao-Yue AU - Chen XY AD - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: iryuoscar@gmail.com. FAU - Chen, Kuan-Yuan AU - Chen KY AD - Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Electronic address: 14388@s.tmu.edu.tw. FAU - Feng, Po-Hao AU - Feng PH AD - Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: fengpohao@tmu.edu.tw. FAU - Lee, Kang-Yun AU - Lee KY AD - Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: leekangyun@tmu.edu.tw. FAU - Fang, Yu-Ting AU - Fang YT AD - Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: crosshine@fda.gov.tw. FAU - Chen, You-Yin AU - Chen YY AD - Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Industrial Ph.D. Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: youyin.chen@gmail.com. FAU - Lo, Yu-Chun AU - Lo YC AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: aricalo@tmu.edu.tw. FAU - Bhavsar, Pankaj K AU - Bhavsar PK AD - National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: p.bhavsar@imperial.ac.uk. FAU - Chung, Kian Fan AU - Chung KF AD - National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: f.chung@imperial.ac.uk. FAU - Chuang, Hsiao-Chi AU - Chuang HC AD - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; National Heart and Lung Institute, Imperial College London, London, UK; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: chuanghc@tmu.edu.tw. LA - eng PT - Journal Article DEP - 20230125 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Galectin 3) RN - 0 (Lipopolysaccharides) RN - 0 (YAP1 protein, human) SB - IM MH - Animals MH - Humans MH - Male MH - Mice MH - Alveolar Epithelial Cells/metabolism MH - Cell Differentiation MH - Galectin 3/metabolism MH - Lipopolysaccharides/pharmacology/metabolism MH - *Lung Injury/metabolism MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells/metabolism MH - Mice, Inbred C57BL MH - *Respiratory Distress Syndrome/therapy/metabolism MH - Umbilical Cord OTO - NOTNLM OT - Alveoli OT - Inflammation OT - Pneumocytes OT - Regeneration OT - Stem cells COIS- Conflict of interest statement The authors declare that they have no conflicts of interest. EDAT- 2023/01/27 06:00 MHDA- 2023/02/08 06:00 CRDT- 2023/01/26 18:14 PHST- 2022/11/07 00:00 [received] PHST- 2023/01/18 00:00 [revised] PHST- 2023/01/20 00:00 [accepted] PHST- 2023/01/27 06:00 [pubmed] PHST- 2023/02/08 06:00 [medline] PHST- 2023/01/26 18:14 [entrez] AID - S0753-3322(23)00090-2 [pii] AID - 10.1016/j.biopha.2023.114302 [doi] PST - ppublish SO - Biomed Pharmacother. 2023 Mar;159:114302. doi: 10.1016/j.biopha.2023.114302. Epub 2023 Jan 25.