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Shanghai, China

Min F.,Shanghai JiaoTong University | Gao F.,Shanghai JianGong Hospital | Liu Z.,Shanghai JiaoTong University
European Review for Medical and Pharmacological Sciences | Year: 2013

BACKGROUND: Acute idiopathic pulmonary fibrosis (IPF) is a serious and progressive form of lung disease, and millions of people suffer from this disease in the world. To provide clues for getting a better understanding of the mechanism of this disease, we identified and further analyzed the differential expressed genes in IPF. METHOD: In this study, we downloaded the gene expression microarray (GSE10667) from Gene Expression Omnibus (GEO) database. The dataset contained a total of 23 samples, including 15 normal controls and 8 diseases samples (IPF). Then, we identified the differentially expressed genes between normal and disease samples with packages in R language. Consequently, the PPI network was also constructed for the products of these DEGs, and modules in the network were analyzed by Cytoscape's plugin Mcode and Bingo. Furthermore, enrichment analysis was performed by DAVID to illustrate the altered pathways in IPF. The drug compounds for PLK1 were screened in DrugBank. RESULTS: Atotal of 349 genes were identified as differentially expressed genes between normal and disease samples, and we constructed a protein-protein interaction network which included 200 pairs of proteins. Then three modules were identified in our network. Function of these modules were predicted to be related to protein kinase binding, extracellular matrix structural and structural constituent of cytoskeleton, respectively. Finally, we focused on module A including 18 DEGs. CONCLUSIONS: PLK1 (Polo like kinge-1) in this module was predicted as a marker gene in IPF, which was related to cell cycle pathway. Several compounds were found which may be the potential drug for IPF. Source

Gao F.,Shanghai JianGong Hospital | Li Q.,Jiangsu University | Hou L.,Shanghai JiaoTong University | Li Z.,Fudan University | And 2 more authors.
Experimental Lung Research | Year: 2014

Background: Acute lung injury (ALI) is a high incidence disease with no effective therapeutic method (mortality rate > 40%). The aim of this study was to find a new and effective therapeutic method for ALI. Methods: After the isolation of human umbilical cord mesenchymal stem cells (HUMSCs) from cesarean fetus, we transfected the HUMSCs with Lenti-ACE2 (angiotensin-converting enzyme 2) viral particles. Then we evaluated the therapeutic effect of HUMSCs harboring ACE2 on ALI, which induced by bleomycin (BLM) in rat model. Results: Our results showed that HUMSCs harboring ACE2 could attenuate ALI degree through reducing pulmonary inflammatory infiltration and degree of vascular permeability, repressing the mRNA level of pro-inflammatory cytokines, activating the mRNA level of anti-inflammatory cytokines and ACE2. Besides, results also demonstrated that HUMSCs harboring ACE2 gene had higher therapeutic effects to ALI than the single factor of HUMSCs or ACE2. Conclusions: This research provided clues for the development of effective therapeutic methods to ALI using stem cell transplantation and gene therapy. © 2014 Informa Healthcare USA, Inc. Source

Liu Z.,Shanghai JiaoTong University | Gao F.,Shanghai JianGong Hospital | Hou L.,Shanghai JiaoTong University | Qian Y.,Shanghai JiaoTong University | Tian R.,Shanghai JiaoTong University
Lung | Year: 2013

Purpose: Acute lung injury (ALI) is characterized by impairment in gas exchange and/or lung mechanics that leads to hypoxemia with the presence of diffuse pulmonary infiltrate. Assessments of lung injury play important roles in the development of rational medical countermeasures. The purpose of this study is to investigate the molecular mechanisms of phosgene-induced lung injury. Methods: We downloaded the gene expression profile of lung tissue from mice exposed to air or phosgene from gene expression omnibus database and identified differentially expressed genes (DEGs) in ALI. Furthermore, we constructed a protein-protein interaction (PPI) network and identified network clusters. Results: In total, 582 DEGs were found and 4 network clusters were identified in the constructed PPI network. Gene set enrichment analysis found that DEGs were mainly involved in mitochondrion organization and biogenesis, mRNA metabolic process, negative regulation of transferase activity or catalytic activity, and coenzyme metabolic process. Pathways of spliceosome, glutathione metabolism, and cell cycle were dysregulated in phosgene-induced ALI. Besides, we identified four genes, including F3, Meis1, Pvf, and Cdc6 in network clusters, which may be used as biomarkers of phosgene-induced ALI. Conclusions: Our results revealed biological processes and pathways involved in phosgene-induced ALI and may expand understandings of phosgene-induced ALI. However, further experiments are needed to confirm our findings. © 2013 Springer Science+Business Media New York. Source

Ji Y.,Shanghai JiaoTong University | Gao F.,Shanghai JianGong Hospital | Sun B.,Shanghai JiaoTong University | Hao J.,Shanghai JiaoTong University | Liu Z.,Shanghai JiaoTong University
Cellular Physiology and Biochemistry | Year: 2015

Background/Aims: Angiotensin converting enzyme 2 (ACE2) has an established role in suppressing the severity of acute lung injury (ALI), especially when it was applied together with transplantation of human umbilical cord mesenchymal stem cells (uMSCs). Although the effects of ACE2 in ALI are believed to mainly result from its role in hydrolyzing angiotensin II (AngII), which subsequently reduces the vascular tension and subsequent pulmonary accumulation of inflammatory cells, we and others have recently reported a possible role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells. However, the underlying mechanisms remain undetermined. Methods: Here, we analyzed the alteration in lung injury severity in ALI after ACE2, by histology and inflammatory cytokine levels. We analyzed apoptosis-associated proteins in lung after ALI, as well as in cultured endothelial cells treated with nitric oxide (NO). We overexpressed SMAD7 to inhibit SMAD2 signaling in cultured endothelial cells and examined its effects on NO-induced cell apoptosis. Results: ACE2 alleviated severity of lung injury after ALI. ACE2 significantly decreased the ALI-induced apoptosis of pulmonary cells in vivo, and ACE2 protected endothelial cells against NO-induced apoptosis in vitro. NO induced phosphorylation of a key factor of transforming growth factor β (TGF β) receptor signaling, SMAD2, which could be dose-dependently inhibited by ACE2. Inhibition of SMAD2 phosphorylation through expression of its inhibitor SMAD7 significantly inhibited NO-induced cell apoptosis, without need for ACE2. Conclusion: Our data suggest that ACE2-mediated AngII degradation may inhibit AngII-mediated SMAD2-phophorylation, possibly through a TGFβ-independent manner, which subsequently suppresses the ALI-induced cell death. Our results thus reveal a novel molecular pathway that controls the pathogenesis of ALI. © 2015 S. Karger AG, Basel. Source

Zhang X.,Shanghai JiaoTong University | Gao F.,Shanghai JianGong Hospital | Li Q.,Jiangsu University | Dong Z.,Shanghai JiaoTong University | And 4 more authors.
Experimental Lung Research | Year: 2015

Purpose: The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). Methods: MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. Results: The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p < 0.05, p < 0.01), while Bcl-2 exhibited an opposite trend. Stem + ACE II performed a better effect than single stem in most indexes, including AI (p < 0.05, p < 0.01). Conclusions: The co-administration of MSCs and ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI. Copyright © 2015 Informa Healthcare USA, Inc. Source

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