FIZZ1 Promotes Airway Remodeling in Asthma Through the PTEN Signaling Pathway
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FIZZ1 Promotes Airway Remodeling in Asthma Through the PTEN Signaling Pathway Jiping Zhao,1 Xingai Jiao,1 Jinxiang Wu,1 Junfei Wang,1 Wenbin Gong,1 Fen Liu,2 Wen Liu,3 Wenxiang Bi,4 and Liang Dong1,5
Abstract—The aim of our study was to elucidate the function and signaling pathway of found in inflammatory zone 1 (FIZZ1) in airway remodeling in asthma. We used a mice model sensitized and challenged by ovalbumin (OVA) to evaluate the expression of FIZZ1, type I collagen, and fibronectin-1 in the airway in asthma. To investigate the signaling pathway regulated by FIZZ1, we treated a cultured murine lung epithelium cell-12 (MLE-12) with FIZZ1 recombination protein, silenced the expression of FIZZ1 with FIZZ1-shRNA in vitro, and then detected phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and expression of type I collagen and fibronectin-1 (FN-1) by Western blotting. In addition, we increased the expression of PTEN by PTEN plasmid transfection then detected the expression of type I collagen and fibronectin-1 in MLE-12 by Western blot analysis and immunofluorescence cytochemistry technology, respectively. First, the expression of FIZZ1, type I collagen, and fibronectin-1 was significantly elevated in the lungs of OVA-challenged mice compared with saline-treated control animals. Secondly, the phosphorylation of PTEN was decreased in MLE-12 treated with FIZZ1 recombination protein in vitro. On the contrary, the phosphorylation of PTEN was increased in MLE-12 cells transfected with FIZZ1-shRNA. Thirdly, results of the Western blot analysis and immunofluorescence cytochemistry showed that expression of type I collagen and fibronectin-1 was increased in cells treated with FIZZ1 recombination protein, while the levels of type I collagen and fibronectin-1 were significantly decreased in cells transfected with PTEN plasmid. FIZZ1 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting FIZZ1 and/or PTEN may be a new therapeutic strategy for asthma. KEY WORDS: asthma; FIZZ1; airway remodeling; PTEN; type I collagen; fibronectin-1.
INTRODUCTION Bronchial asthma is a chronic lung disease which is characterized by chronic airway inflammation, smooth
Jiping Zhao and Xingai Jiao contributed equally to this work. 1
Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China 2 Department of Pulmonary Medicine, Shandong Provincial Qianfoshan Hospital, Jinan 250014, People’s Republic of China 3 Department of Pulmonary Medicine, The Second Hospital of Shandong University, Jinan 250100, People’s Republic of China 4 Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, People’s Republic of China 5 To whom correspondence should be addressed at Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China. E-mail: [email protected]
muscle dysfunction, and airway remodeling [1]. More recently, it has become clear that airwa
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