YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

Xiao Yue Chen; Kuan Yuan Chen; Po Hao Feng; Kang Yun Lee; Yu Ting Fang; You Yin Chen; Yu Chun Lo; Pankaj K. Bhavsar; Kian Fan Chung; Hsiao Chi Chuang

doi:10.1016/j.biopha.2023.114302

YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

Xiao Yue Chen, Kuan Yuan Chen, Po Hao Feng, Kang Yun Lee, Yu Ting Fang, You Yin Chen, Yu Chun Lo, Pankaj K. Bhavsar, Kian Fan Chung, Hsiao Chi Chuang

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Article number	114302
Journal	Biomedicine and Pharmacotherapy
Volume	159
DOIs	https://doi.org/10.1016/j.biopha.2023.114302
Publication status	Published - Mar 2023

Keywords

Alveoli
Inflammation
Pneumocytes
Regeneration
Stem cells

ASJC Scopus subject areas

Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.biopha.2023.114302

Cite this

Chen, X. Y., Chen, K. Y., Feng, P. H., Lee, K. Y., Fang, Y. T., Chen, Y. Y., Lo, Y. C., Bhavsar, P. K., Chung, K. F., & Chuang, H. C. (2023). YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome. Biomedicine and Pharmacotherapy, 159, Article 114302. https://doi.org/10.1016/j.biopha.2023.114302

Chen, XY, Chen, KY , Feng, PH , Lee, KY, Fang, YT, Chen, YY, Lo, YC, Bhavsar, PK, Chung, KF & Chuang, HC 2023, 'YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome', Biomedicine and Pharmacotherapy, vol. 159, 114302. https://doi.org/10.1016/j.biopha.2023.114302

@article{74571495b3d748e8a15c95246a0c4b67,

title = "YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome",

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.",

keywords = "Alveoli, Inflammation, Pneumocytes, Regeneration, Stem cells",

author = "Chen, {Xiao Yue} and Chen, {Kuan Yuan} and Feng, {Po Hao} and Lee, {Kang Yun} and Fang, {Yu Ting} and Chen, {You Yin} and Lo, {Yu Chun} and Bhavsar, {Pankaj K.} and Chung, {Kian Fan} and Chuang, {Hsiao Chi}",

note = "Funding Information: This study was funded by the National of Science and Technology Council of Taiwan ( 109–2314-B-038–093-MY3 and 111–2314-B-038–079 ) and partially supported by a grant from Meridigen Biotech Co., Ltd., Taipei , Taiwan ( 2018-RD-VIV-002 ). Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

doi = "10.1016/j.biopha.2023.114302",

language = "English",

volume = "159",

journal = "Biomedicine and Pharmacotherapy",

issn = "0753-3322",

publisher = "Elsevier Masson",

}

TY - JOUR

T1 - YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

AU - Chen, Xiao Yue

AU - Chen, Kuan Yuan

AU - Feng, Po Hao

AU - Lee, Kang Yun

AU - Fang, Yu Ting

AU - Chen, You Yin

AU - Lo, Yu Chun

AU - Bhavsar, Pankaj K.

AU - Chung, Kian Fan

AU - Chuang, Hsiao Chi

N1 - Funding Information: This study was funded by the National of Science and Technology Council of Taiwan ( 109–2314-B-038–093-MY3 and 111–2314-B-038–079 ) and partially supported by a grant from Meridigen Biotech Co., Ltd., Taipei , Taiwan ( 2018-RD-VIV-002 ). Publisher Copyright: © 2023 The Authors

PY - 2023/3

Y1 - 2023/3

N2 - 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.

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 (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.

KW - Alveoli

KW - Inflammation

KW - Pneumocytes

KW - Regeneration

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=85146641772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85146641772&partnerID=8YFLogxK

U2 - 10.1016/j.biopha.2023.114302

DO - 10.1016/j.biopha.2023.114302

M3 - Article

AN - SCOPUS:85146641772

SN - 0753-3322

VL - 159

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

M1 - 114302

ER -

YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this