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Protective effect of HSF1 on mice with LPS-induced acute lung injury and screening of relevant differentially-expressed genes
Authors:XIAO Gui  WANG Gui-liang  CHEN Guang-wen  WANG Xiao-li  ZHANG Hua-li  WANG Kang-kai  LIU Mei-dong  LIU Ke  XIAO Xian-zhong
Institution:1. Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410008, China; 2. Department of International School of Nursing, Hainan Medical University, Haikou 571199, China; 3. Digestion Department of Gannan Medical University Pingxiang Hospital, Pingxiang 337000, China
Abstract:AIM: To study the protective effect of heat shock factor1 (HSF1) on the mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI), and to screen the relevant differentially-expressed genes. METHODS: ALI mouse model was established by LPS intracheal instillation. The macroscopic and pathological changes of the lung tissue were observed, and the concentrations of total protein, TNF-α, IL-β, IL-6 and VEGF in the bronchoalveolar lavage fluid (BALF) were analyzed. Differentially-expressed genes in the lung tissues of HSF1+/+ mice and HSF1-/- mice with ALI induced by LPS were screened by gene chips. The key gene was verified by real-time qPCR. RESULTS: The macroscopic and pathological changes of the lung injury in HSF1-/-+LPS mice were more serious than those in HSF1+/++LPS mice. The concentrations of total protein, VEGF, TNF-α, IL-1β and IL-6 in the BALF of HSF1-/-+LPS mice were significantly higher than those of HSF1+/++LPS mice (P<0.05). Compared with the HSF1+/+ mice, a total of 918 differentially-expressed genes were indentified in the HSF1-/- mice, among which the expression levels of 65 genes had obvious diffe-rence, with 28 genes up-regulated, including Atg7, ccr1, cxcr2, Tbl1xr1, Mmp9, Pparg, Plcb2, Arrb2, Cntn1, Col4a6, etc, and 37 genes down-regulated, including Fgfr1, Fgfr2, Map4k4, Ddx58, Tfg, Stat3, Smad4, Lamc1, Sdc3, etc. The results of real-time qPCR showed that the mRNA level of CXCR2 in HSF1-/-+ LPS mice was significantly higher than that in HSF1+/++ LPS mice, which was consistent with the results of gene chips. CONCLUSION: HSF1 has protective effect on the mice with LPS-induced ALI. CXCR2 may be involved in the protective effect of HSF1 on this process.
Keywords:Acute lung injury  Heat shock factor 1  Gene chips  Differential gene expression  
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