title: Calpain 1 regulates TGF-β1-induced epithelial-mesenchymal transition in human lung epithelial cells via PI3K/Akt signaling pathway.
abstract: Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-β1 (TGF-β1), TGF-β1 + PD 150606 (a calpain 1 inhibitor), or PD 150606. We examined E-cadherin (E-cad), α-smooth muscle actin (α-SMA), and calpain 1 mRNA transcript and protein expression levels in these four groups by performing RT-PCR and western blot analyses. The results indicated that TGF-β1 treatment significantly downregulated E-cad and upregulated α-SMA expression compared with that of the blank control group (P<0.05). TGF-β1 also enhanced calpain 1 expression compared with that of the blank control group (P<0.05). By contrast, treatment with the calpain 1 inhibitor PD 150606 increased E-cad expression and decreased α-SMA expression. Furthermore, PD 150606 treatment antagonized TGF-β1-mediated increase in Akt/phospho-Akt in A549 epithelial cells. However, TGF-β1-induced ETM was not correlated with the ERK and JNK signaling pathways. These combined results indicate that calpain 1 could regulate EMT in TGF-β1-treated A549 epithelial cells via the PI3K/Akt signaling pathway.
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lian
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Zhen-Shun
authors.initials: ZS
authors.lastname: Cheng
keywords: Idiopathic pulmonary fibrosis; PI3K/Akt signaling; calpain 1; epithelial-mesenchymal transition (EMT); transforming growth factor-β1 (TGF-β1)