title: Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs.
abstract: Radiation-induced lung injury (RILI) is a common complication associated with thoracic radiotherapy. The aim of the present study was to investigate the effects of a single 15-Gy dose of right-thoracic lung irradiation on the expression levels of matrix metalloproteinases (MMPs) and other proteins in the alveolar epithelial type II (AE2) cells of Bama minipigs. All minipigs received either right-thoracic irradiation or sham irradiation under anesthesia, and were sacrificed at 4, 8, 12 or 24 weeks after irradiation. Collagen deposition was measured using Massons trichrome staining. Surfactant protein A (SP-A), transforming growth factor β1 (TGFβ1), MMP2, MMP9, vimentin and E-cadherin protein expression levels were evaluated using western blot analysis, and the MMP2 and MMP9 gelatinase activities were tested using gelatin zymography. SP-A and α-smooth muscle actin (α-SMA) co-localization was visualized using double immunofluorescence staining. At each time-point following irradiation, a significant increase in TGFβ1, α-SMA, MMP2, MMP9 and vimentin protein expression levels and MMP2 and MMP9 gelatinase activity were observed in the irradiated lungs compared with the sham-irradiated controls. By contrast, SP-A and E-cadherin protein expression levels decreased in a time-dependent manner post-irradiation. SP-A and α-SMA co-localization was observed in irradiated alveolar epithelial cells. These data demonstrate that E-cadherin, SP-A, MMP2 and MMP9 may function as sensitive predictors of RILI. Epithelial-mesenchymal transition (EMT) occurs in the irradiated lungs of Bama minipigs, and MMP2 and MMP9 may contribute to EMT in AE2 cells by regulating TGFβ1. Therefore, EMT may serve a crucial function in the development of RILI.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Yue
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Guangxi Province Maternity and Child Care Hospital, Nanning, Guangxi 530002, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Rensheng
authors.initials: R
authors.lastname: Wang
keywords: epithelial-mesenchymal transition; matrix metalloproteinase-2; matrix metalloproteinase-9; minipigs; radiation-induced lung injury