title: FIZZ1 Promotes Airway Remodeling in Asthma Through the PTEN Signaling Pathway.
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.
authors: Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.
authors: Jiping
authors: J
authors: Zhao
authors: Xingai
authors: X
authors: Jiao
authors: Jinxiang
authors: J
authors: Wu
authors: Junfei
authors: J
authors: Wang
authors: Wenbin
authors: W
authors: Gong
authors: Fen
authors: F
authors: Liu
authors: Wen
authors: W
authors: Liu
authors: Wenxiang
authors: W
authors: Bi
authors: Liang
authors: L
authors: Dong
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C413576:Retnla protein, mouse; D010047:Ovalbumin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
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