Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice

Kuniko Nakajima, Michio Ono, Uros S. Radovic, Selma Dizdarevic, Shin Ichi Tomizawa, Kazushige Kuroha, Go Nagamatsu, Ikue Hoshi, Risa Matsunaga, Takayuki Shirakawa, Takeyuki Kurosawa, Yasunari Miyazaki, Asahide Seki, Yutaka Suzuki, Haruhiko Koseki, Masataka Nakamura, Toshio Suda, Kazuyuki Ohbo

研究成果: ジャーナルへの寄稿記事

抄録

Respiratory failure is a life-threatening problem for pre-term and term infants, yet many causes remain unknown. Here, we present evidence that whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (Wfdc2), a protease inhibitor previously unrecognized in respiratory disease, may be a causal factor in infant respiratory failure. Wfdc2 transcripts are detected in the embryonic lung and analysis of a Wfdc2-GFP knock-in mouse line shows that both basal and club cells, and type II alveolar epithelial cells (AECIIs), express Wfdc2 neonatally. Wfdc2-null-mutant mice display progressive atelectasis after birth with a lethal phenotype. Mutant lungs have multiple defects, including impaired cilia and the absence of mature club cells from the tracheobronchial airways, and malformed lamellar bodies in AECIIs. RNA sequencing shows significant activation of a pro-inflammatory pathway, but with low-quantity infiltration of mononuclear cells in the lung. These data demonstrate that Wfdc2 function is vitally important for lung aeration at birth and that gene deficiency likely causes failure of the lung mucosal barrier.

元の言語英語
記事番号dmm.040139
ジャーナルDMM Disease Models and Mechanisms
12
発行部数11
DOI
出版物ステータス出版済み - 1 1 2019

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Protease Inhibitors
Respiratory Insufficiency
Disulfides
Cause of Death
Lung
Pulmonary diseases
Infiltration
Genes
Chemical activation
RNA
Defects
Parturition
RNA Sequence Analysis
Alveolar Epithelial Cells
Pulmonary Atelectasis
Cilia
whey acidic proteins
Perinatal Death
Phenotype
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice. / Nakajima, Kuniko; Ono, Michio; Radovic, Uros S.; Dizdarevic, Selma; Tomizawa, Shin Ichi; Kuroha, Kazushige; Nagamatsu, Go; Hoshi, Ikue; Matsunaga, Risa; Shirakawa, Takayuki; Kurosawa, Takeyuki; Miyazaki, Yasunari; Seki, Asahide; Suzuki, Yutaka; Koseki, Haruhiko; Nakamura, Masataka; Suda, Toshio; Ohbo, Kazuyuki.

:: DMM Disease Models and Mechanisms, 巻 12, 番号 11, dmm.040139, 01.01.2019.

研究成果: ジャーナルへの寄稿記事

Nakajima, K, Ono, M, Radovic, US, Dizdarevic, S, Tomizawa, SI, Kuroha, K, Nagamatsu, G, Hoshi, I, Matsunaga, R, Shirakawa, T, Kurosawa, T, Miyazaki, Y, Seki, A, Suzuki, Y, Koseki, H, Nakamura, M, Suda, T & Ohbo, K 2019, 'Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice', DMM Disease Models and Mechanisms, 巻. 12, 番号 11, dmm.040139. https://doi.org/10.1242/dmm.040139
Nakajima, Kuniko ; Ono, Michio ; Radovic, Uros S. ; Dizdarevic, Selma ; Tomizawa, Shin Ichi ; Kuroha, Kazushige ; Nagamatsu, Go ; Hoshi, Ikue ; Matsunaga, Risa ; Shirakawa, Takayuki ; Kurosawa, Takeyuki ; Miyazaki, Yasunari ; Seki, Asahide ; Suzuki, Yutaka ; Koseki, Haruhiko ; Nakamura, Masataka ; Suda, Toshio ; Ohbo, Kazuyuki. / Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice. :: DMM Disease Models and Mechanisms. 2019 ; 巻 12, 番号 11.
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AU - Dizdarevic, Selma

AU - Tomizawa, Shin Ichi

AU - Kuroha, Kazushige

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AU - Hoshi, Ikue

AU - Matsunaga, Risa

AU - Shirakawa, Takayuki

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AU - Miyazaki, Yasunari

AU - Seki, Asahide

AU - Suzuki, Yutaka

AU - Koseki, Haruhiko

AU - Nakamura, Masataka

AU - Suda, Toshio

AU - Ohbo, Kazuyuki

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