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PAI-1 regulates AT2-mediated re-alveolarization and ion permeability
被引:3
作者:

Ali, Gibran
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Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

Zhang, Mo
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Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA
Xinxiang Med Univ, Xinxiang, Henan, Peoples R China Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

Chang, Jianjun
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Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

Zhao, Runzhen
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机构:
Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA
Loyola Univ Chicago, Burn & Shock Trauma Res Inst, Dept Surg, 2160 S 1St Ave, Maywood, IL 60153 USA Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

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Zhang, Jiwang
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Loyola Univ Med Ctr, Oncol Inst, Cardinal Bernardin Canc Ctr, Dept Canc Biol, Maywood, IL USA Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

Ji, Hong-Long
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机构:
Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA
Loyola Univ Chicago, Burn & Shock Trauma Res Inst, Dept Surg, 2160 S 1St Ave, Maywood, IL 60153 USA Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA
机构:
[1] Univ Texas Tyler Hlth Sci Ctr, Texas Lung Injury Inst, Dept Cellular & Mol Biol, Tyler, TX 75708 USA
[2] Xinxiang Med Univ, Xinxiang, Henan, Peoples R China
[3] Boston Univ, Dept Med, Div Pulm & Crit Care Med, Boston, MA USA
[4] Loyola Univ Med Ctr, Oncol Inst, Cardinal Bernardin Canc Ctr, Dept Canc Biol, Maywood, IL USA
[5] Loyola Univ Chicago, Burn & Shock Trauma Res Inst, Dept Surg, 2160 S 1St Ave, Maywood, IL 60153 USA
基金:
美国国家卫生研究院;
关键词:
Serpine1;
Proliferation;
Differentiation;
Organoids;
Re-alveolarization;
PLASMINOGEN-ACTIVATOR INHIBITOR-1;
EPITHELIAL SODIUM-CHANNELS;
FIBROBLAST APOPTOSIS;
PULMONARY-FIBROSIS;
LUNG;
CELL;
FIBRINOLYSIS;
PATHOGENESIS;
COAGULATION;
STRESS;
D O I:
10.1186/s13287-023-03414-4
中图分类号:
Q813 [细胞工程];
学科分类号:
摘要:
Background Acute lung injury is characterized by overwhelmingly elevated PAI-1 in both lung edema fluid and the circulating system. The role of increased PAI-1, encoded by Serpine1 gene, in the regeneration of injured lung epithelium has not been understood completely. This study aimed to investigate the role of Serpine1 in the regulation of alveolar type 2 epithelial cell (AT2) fate in a humanized mouse line carrying diseased mutants (Serpine1(Tg)). Methods Wild-type (wt) and Serpine1(Tg) AT2 cells were either cultured as monolayers or 3D alveolospheres. Colony-forming assay and total surface area of organoids were analyzed. AT1 and AT2 cells in organoids were counted by immunohistochemistry and fluorescence-activated cell sorting (FACS). To test the potential effects of elevated PAI-1 on the permeability in the epithelial monolayers, we digitized the biophysical properties of polarized AT2 monolayers grown at the air-liquid interface. Results A significant reduction in total AT2 cells harvested in Serpine1(Tg) mice was observed compared with wt controls. AT2 cells harvested from Serpine1(Tg) mice reduced significantly over the wt controls. Spheroids formed by Serpine1(Tg) AT2 cells were lesser than wt control. Similarly, the corresponding surface area, a readout of re-alveolarization of injured epithelium, was markedly reduced in Serpine1(Tg) organoids. FACS analysis revealed a significant suppression in the number of AT2 cells, in particular, the CD44(+) subpopulation, in Serpine1(Tg) organoids. A lesser ratio of AT1:AT2 cells in Serpine1(Tg) organoids was observed compared with wt cultures. There was a significant increase in transepithelial resistance but not amiloride inhibition. Conclusions Our study suggests elevated PAI-1 in injured lungs downregulates alveolar epithelial regeneration by reducing the AT2 self-renewal, particularly in the CD44(+) cells.
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论文数: 0 引用数: 0
h-index: 0
机构: Erie Cty Med Ctr & Labs, Div Pulm Crit Care & Sleep Med, Buffalo, NY 14215 USA
[10]
Plasminogen activator inhibitor 1 - insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence
[J].
Elzi, David J.
;
Lai, Yanlai
;
Song, Meihua
;
Hakala, Kevin
;
Weintraub, Susan T.
;
Shiio, Yuzuru
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2012, 109 (30)
:12052-12057

Elzi, David J.
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机构:
Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

Lai, Yanlai
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h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

Song, Meihua
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

Hakala, Kevin
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

Weintraub, Susan T.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA
Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

Shiio, Yuzuru
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA
Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA
Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA