Han-Di Liao1, Yong Mao1, You-Guo Ying1. 1. Department of Intensive Care Unit, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China.
Abstract
INTRODUCTION: The central objective of the study was to determine the possibility and potential mechanism by which the laminin-integrin α7β1 signaling pathway acts on mechanical ventilation (MV)-induced pulmonary fibrosis in a rat model. METHODS: Fibrosis rat models were established via the mechanical injury method. Ninety rats were recruited and divided into the normal, low tidal volume (LVT), huge VT (HVT), Arg-Gly-Asp-Ser (RGDS), LVT + RGDS and HVT + RGDS groups. On day 0, 3, and 7 after model establishment, the pulmonary hydroxyproline content was measured using alkaline hydrolysis and the pulmonary index was also calculated. All rats in each group were executed on day 0, 3 and 7. The histopathological changes detected in the left pulmonary tissues were observed using hematoxylin-eosin (HE) and Masson staining methods. DISCUSSION: The mRNA and protein expressions of Wnt-5A, β-catenin, E-cadherin and Collagen I in the Wnt/β-catenin signaling pathway were detected using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting methods. Immunohistochemistry was employed to detect the fibronectin (FN) expression in the pulmonary tissues on the 7th day. All indexes in the RGDS and LVT + RGDS groups indicated no explicit differences compared with the normal group. In the LVT, HVT, HVT + RGDS groups, the respective weights of the rats and the expression of E-cadherin on the 7th day exhibited decreases, however the pulmonary index, hydroxyproline, pulmonary alveolar inflammation, pulmonary fibrosis, FN expression, and protein expressions of Wnt-5A, β-catenin, and Collagen I all displayed increased levels (all P<0.05). The index changes detected in the HVT group were the most blatant results observed in the study. The rat pulmonary index on the 7th day, hydroxyproline (HYP), pulmonary alveolar inflammation, pulmonary fibrosis, FN expression, and protein expressions of Wnt-5A, β-catenin, and type I-collagen were all down-regulated, in contrast the expression of E-cadherin was up-regulated in the LVT + RGDS and HVT + RGDS groups in comparison with the LVT and HVT groups, respectively (all P<0.05). CONCLUSIONS: The findings of the study suggested that RGDS could act to block the laminin-integrin α7β1-signaling pathway, ultimately contributing to the inhibition of the progression of MV-induced pulmonary fibrosis.
INTRODUCTION: The central objective of the study was to determine the possibility and potential mechanism by which the laminin-integrin α7β1 signaling pathway acts on mechanical ventilation (MV)-induced pulmonary fibrosis in a rat model. METHODS: Fibrosis rat models were established via the mechanical injury method. Ninety rats were recruited and divided into the normal, low tidal volume (LVT), huge VT (HVT), Arg-Gly-Asp-Ser (RGDS), LVT + RGDS and HVT + RGDS groups. On day 0, 3, and 7 after model establishment, the pulmonary hydroxyproline content was measured using alkaline hydrolysis and the pulmonary index was also calculated. All rats in each group were executed on day 0, 3 and 7. The histopathological changes detected in the left pulmonary tissues were observed using hematoxylin-eosin (HE) and Masson staining methods. DISCUSSION: The mRNA and protein expressions of Wnt-5A, β-catenin, E-cadherin and Collagen I in the Wnt/β-catenin signaling pathway were detected using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting methods. Immunohistochemistry was employed to detect the fibronectin (FN) expression in the pulmonary tissues on the 7th day. All indexes in the RGDS and LVT + RGDS groups indicated no explicit differences compared with the normal group. In the LVT, HVT, HVT + RGDS groups, the respective weights of the rats and the expression of E-cadherin on the 7th day exhibited decreases, however the pulmonary index, hydroxyproline, pulmonary alveolar inflammation, pulmonary fibrosis, FN expression, and protein expressions of Wnt-5A, β-catenin, and Collagen I all displayed increased levels (all P<0.05). The index changes detected in the HVT group were the most blatant results observed in the study. The rat pulmonary index on the 7th day, hydroxyproline (HYP), pulmonary alveolar inflammation, pulmonary fibrosis, FN expression, and protein expressions of Wnt-5A, β-catenin, and type I-collagen were all down-regulated, in contrast the expression of E-cadherin was up-regulated in the LVT + RGDS and HVT + RGDS groups in comparison with the LVT and HVT groups, respectively (all P<0.05). CONCLUSIONS: The findings of the study suggested that RGDS could act to block the laminin-integrin α7β1-signaling pathway, ultimately contributing to the inhibition of the progression of MV-induced pulmonary fibrosis.
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