TACE in perinatal mouse lung epithelial cells promotes lung saccular formation

Wei Xu, Chengyu Liu, Vesa Kaartinen, Hui Chen, Chi Han Lu, Wenming Zhang, Yongfeng Luo, Wei Shi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tumor necrosis factor-a converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyo-cytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume305
Issue number12
DOIs
StatePublished - Dec 15 2013

Fingerprint

Tumor Necrosis Factor-alpha
Epithelial Cells
Lung
Enzymes
Knockout Mice
Multiple Abnormalities
Mesoderm
Cell Differentiation
Myocardium
Epithelium
Cell Proliferation
Cell Membrane

Keywords

  • Lung development
  • Tumor necrosis factor-α converting enzyme

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

TACE in perinatal mouse lung epithelial cells promotes lung saccular formation. / Xu, Wei; Liu, Chengyu; Kaartinen, Vesa; Chen, Hui; Lu, Chi Han; Zhang, Wenming; Luo, Yongfeng; Shi, Wei.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 305, No. 12, 15.12.2013.

Research output: Contribution to journalArticle

Xu, Wei ; Liu, Chengyu ; Kaartinen, Vesa ; Chen, Hui ; Lu, Chi Han ; Zhang, Wenming ; Luo, Yongfeng ; Shi, Wei. / TACE in perinatal mouse lung epithelial cells promotes lung saccular formation. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2013 ; Vol. 305, No. 12.
@article{6254c935727a47d98fc805b617e13152,
title = "TACE in perinatal mouse lung epithelial cells promotes lung saccular formation",
abstract = "Tumor necrosis factor-a converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyo-cytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.",
keywords = "Lung development, Tumor necrosis factor-α converting enzyme",
author = "Wei Xu and Chengyu Liu and Vesa Kaartinen and Hui Chen and Lu, {Chi Han} and Wenming Zhang and Yongfeng Luo and Wei Shi",
year = "2013",
month = "12",
day = "15",
doi = "10.1152/ajplung.00189.2013",
language = "English (US)",
volume = "305",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "12",

}

TY - JOUR

T1 - TACE in perinatal mouse lung epithelial cells promotes lung saccular formation

AU - Xu, Wei

AU - Liu, Chengyu

AU - Kaartinen, Vesa

AU - Chen, Hui

AU - Lu, Chi Han

AU - Zhang, Wenming

AU - Luo, Yongfeng

AU - Shi, Wei

PY - 2013/12/15

Y1 - 2013/12/15

N2 - Tumor necrosis factor-a converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyo-cytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.

AB - Tumor necrosis factor-a converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyo-cytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.

KW - Lung development

KW - Tumor necrosis factor-α converting enzyme

UR - http://www.scopus.com/inward/record.url?scp=84890324905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890324905&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00189.2013

DO - 10.1152/ajplung.00189.2013

M3 - Article

VL - 305

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 12

ER -