Wang Junfei, Li Fei, Yang Mengmeng, Wu Jinxiang, Zhao Jiping, Gong Wenbin, Liu Wen, Bi Wenxiang, Dong Liang
Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China ; Department of Pulmonary Medicine, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China.
Exp Ther Med. 2014 May;7(5):1265-1270. doi: 10.3892/etm.2014.1580. Epub 2014 Feb 24.
Found in inflammatory zone 1 (FIZZ1) plays a vital role in pulmonary inflammation and angiogenesis. In addition, FIZZ1 plays a role in the early stages of airway remodeling in asthma by increasing the expression of α smooth muscle actin (α-SMA) and type I collagen. However, the role of FIZZ1 in the airway remodeling of asthma remains unclear. In the present study, FIZZ1 was identified to be upregulated in ovalbumin (OVA)-induced asthmatic mice, along with phosphorylated protein kinase B (Akt). Following FIZZ1 recombinant protein co-culture in the murine lung epithelial-cell line, Akt phosphorylation was upregulated, however, following transfection with FIZZ1-small hairpin RNA, the phosphorylation levels were decreased. The variation in α-SMA and type I collagen expression levels was consistent with the Akt phosphorylation levels. Intratracheal administration of LY294002 and Akt inhibitor IV to the asthmatic mice was capable of reducing airway inflammation, downregulating the expression of α-SMA, type I collagen and fibronectin-1 and increasing the expression of E-cadherin. In conclusion, the present study demonstrated that FIZZ1 promoted airway remodeling in asthma via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt signaling pathway may attenuate the early stages of airway remodeling induced by OVA by regulating the abnormal process of epithelial-mesenchymal transition.
炎症区域1发现蛋白（FIZZ1）在肺部炎症和血管生成中起着至关重要的作用。此外，FIZZ1通过增加α平滑肌肌动蛋白（α-SMA）和I型胶原蛋白的表达，在哮喘气道重塑的早期阶段发挥作用。然而，FIZZ1在哮喘气道重塑中的作用仍不清楚。在本研究中，发现FIZZ1在卵清蛋白（OVA）诱导的哮喘小鼠中上调，同时磷酸化蛋白激酶B（Akt）也上调。在将FIZZ1重组蛋白与小鼠肺上皮细胞系共培养后，Akt磷酸化上调，然而，在用FIZZ1小发夹RNA转染后，磷酸化水平降低。α-SMA和I型胶原蛋白表达水平的变化与Akt磷酸化水平一致。向哮喘小鼠气管内注射LY-294002和Akt抑制剂IV能够减轻气道炎症，下调α-SMA、I型胶原蛋白和纤连蛋白-1的表达，并增加E-钙黏蛋白的表达。总之，本研究表明FIZZ1通过磷酸肌醇3激酶（PI3K）/Akt信号通路促进哮喘气道重塑。阻断PI3K/Akt信号通路可能通过调节上皮-间质转化的异常过程来减轻OVA诱导的气道重塑早期阶段。
