Matrix Metalloproteinase 7 Expression and Apical Epithelial Defects in Atp8b1 Mutant Mouse Model of Pulmonary Fibrosis

被引：4

作者：

Westermann-Clark, Emma ^{[1
,2
,3
]}

Soundararajan, Ramani ^{[1
]}

Fukumoto, Jutaro ^{[1
]}

Patil, Sahebgowda Sidramagowda ^{[1
]}

Stearns, Timothy M. ^{[4
]}

Saji, Smita ^{[1
]}

Czachor, Alexander ^{[1
]}

Hernandez-Cuervo, Helena ^{[1
]}

Breitzig, Mason ^{[1
]}

Krishnamurthy, Sudarshan ^{[1
,5
]}

Lockey, Richard F. ^{[1
]}

Kolliputi, Narasaiah ^{[1
]}

机构：

[1] Univ South Florida Morsani, Coll Med, Dept Internal Med, Div Allergy Immunol,Lab Dr Narasaiah Kolliputi, Tampa, FL 33612 USA

[2] Univ S Florida, Coll Med, Dept Med, Div Allergy Immunol, Tampa, FL 33612 USA

[3] Univ S Florida, Coll Med, Dept Pediat, Div Allergy Immunol, Tampa, FL 33612 USA

[4] MDI Biol Lab, Salsbury Cove, ME 04672 USA

[5] Wake Forest Sch Med, Bowman Gray Ctr Med Educ, Winston Salem, NC 27101 USA

来源：

BIOMOLECULES | 2022年 / 12卷 / 02期

基金：

美国国家卫生研究院;

关键词：

idiopathic pulmonary fibrosis; Atp8b1; mutant; MMP7; apical; ciliogenesis; INJURY; MMP-7; DIFFERENTIATION; CARDIOLIPIN; BIOMARKERS; MATRILYSIN; DIAGNOSIS;

D O I：

10.3390/biom12020283

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Abnormalities in airway epithelia and lung parenchyma are found in Atp8b1 mutant mice, which develop pulmonary fibrosis after hyperoxic insult. Microarray and ingenuity pathway analysis (IPA) show numerous transcripts involved in ciliogenesis are downregulated in 14-month (14 M) -old Atp8b1 mouse lung compared with wild-type C57BL/6. Lung epithelium of Atp8b1 mice demonstrate apical abnormalities of ciliated and club cells in the bronchial epithelium on transmission electron microscopy (TEM). Matrix metalloproteinase 7 (MMP7) regulates of ciliogenesis and is a biomarker for idiopathic pulmonary fibrosis (IPF) in humans. Mmp7 transcript and protein expression are significantly upregulated in 14 M Atp8b1 mutant mouse lung. MMP7 expression is also increased in bronchoalveolar lavage fluid (BAL). Immunohistochemistry is localized MMP7 to bronchial epithelial cells in the Atp8b1 mutant. In conclusion, MMP7 is upregulated in the aged Atp8b1 mouse model, which displays abnormal ciliated cell and club cell morphology. This mouse model can facilitate the exploration of the role of MMP7 in epithelial integrity and ciliogenesis in IPF. The Atp8b1 mutant mouse is proposed as a model for IPF.

引用

页数：11

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