Laboratory Investigation - Table of Contents alert Volume 95 Issue 8

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TABLE OF CONTENTS Volume 95, Issue 8 (August 2015) In this issue Inside the USCAP Journals Research Articles Also new AOP Sign up for e-alerts Recommend to your library Web feed Subscribe Inside the USCAP Journals Top Inside the USCAP Journals 2015 95: 844-845; 10.1038/labinvest.2015.92 Full Text Research Articles Top ANGIOGENESIS, CARDIOVASCULAR AND PULMONARY SYSTEMS Rapamycin increases CCN2 expression of lung fibroblasts via phosphoinositide 3-kinase In this paper, the authors show that rapamycin significantly augments basal or transforming growth factor (TGF)-β1-induced connective tissue growth factor expression in normal and fibrotic human lung fibroblasts via activation of the phosphatidyl-inositol-3-kinase (PI3K)-AKT pathway. Rapamcin has no antifibrotic effect and in some cases, even promotes the generation of fibrotic lesions. Combined inhibition of PI3K and mTOR may be a more effective regime for antifibrotic treatment. Xuefeng Xu, Huaping Dai, Jing Geng, Xuan Wan, Xiaoxi Huang, Fei Li, Dianhua Jiang and Chen Wang 2015 95: 846-859; advance online publication, July 20, 2015; 10.1038/labinvest.2015.68 Abstract | Full Text Cardioprotection by PI3K-mediated signaling is required for anti-arrhythmia and myocardial repair in response to ischemic preconditioning in infarcted pig hearts The mechanism by which phosphatidyl-inositol-3-kinase (PI3K)/AKT confers the anti-arrhythmic effects that occur in response to ischemic preconditioning is not clear. This study suggests that ischemic preconditioning reduces ventricular arrhythmia, improves myocardial remodeling and cardiac repair following acute myocardial infarction via upregulation of PI3K/AKT-mediated expression of connexin 43 and proangiogenic factors. Feng Su, Lan Zhao, Shaoheng Zhang, Jiahong Wang, Nannan Chen, Qunlin Gong, Jinhui Tang, Hao Wang, Jianhua Yao, Qin Wang, Ming Zhong and Jian Yan 2015 95: 860-871; advance online publication, June 1, 2015; 10.1038/labinvest.2015.64 Abstract | Full Text Role of α1 and α2 chains of type IV collagen in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts Type IV collagen α1 and α2 chains are deposited in early fibrotic lesions of usual interstitial pneumonia but not organizing pneumonia. This paper shows that type IV collagen produced by fibroblasts inhibits their migration via the focal adhesion kinase pathway. Type IV collagen in early fibrotic lesions may therefore be implicated in refractory pathophysiology of usual interstitial pneumonia and may be a target for the treatment of idiopathic interstitial pneumonias. Hirokazu Urushiyama, Yasuhiro Terasaki, Shinya Nagasaka, Mika Terasaki, Shinobu Kunugi, Takahide Nagase, Yuh Fukuda and Akira Shimizu 2015 95: 872-885; advance online publication, May 25, 2015; 10.1038/labinvest.2015.66 Abstract | Full Text Bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (iBALT) This study reveals that the ovalbumin mouse model of asthma has features of immune complex disease which cast doubt on its validity as a model for asthma. Unlike human acute asthma, the lesions of the experimental mouse model are not initiated by mast cell degranulation but by immune complex eosinophilic vasculitis. Although serum IgE is elevated, mast cells are only found in the most proximal part of the main stem bronchus and are not seen in the distal bronchus or peripheral lung. Ian C Guest and Stewart Sell 2015 95: 886-902; advance online publication, June 1, 2015; 10.1038/labinvest.2015.72 Abstract | Full Text HEPATIC AND PANCREATIC SYSTEMS TGFβ1 exacerbates blood–brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5 In this paper, an animal model of hepatic encephalopathy was used to examine vasogenic brain edema following acute liver failure. Increased blood-brain barrier permeability is observed in the model, which is reduced by inhibition of TGFβ1. The increased endothelial cell permeability is generated by TGFβ1 via SMAD3-dependent signaling, which upregulates matrix metalloproteinase-9 and downregulates claudin-5. TGFβ1 therefore contributes to the pathology of acute liver failure by promoting blood-brain barrier permeability. Matthew A McMillin, Gabriel A Frampton, Andrew P Seiwell, Nisha S Patel, Amber N Jacobs and Sharon DeMorrow 2015 95: 903-913; advance online publication, June 1, 2015; 10.1038/labinvest.2015.70 Abstract | Full Text The role of iNOS in cholesterol-induced liver fibrosis The role of inducible nitric oxide synthase (iNOS) in liver fibrosis caused by a high cholesterol diet (HCD) is determined in this study. Pharmacological inhibition of iNOS during HCD feeding reduces fibrosis, and iNOS-deficient mice exhibit decreased hypoxia inducible factor 1 and matrix metalloproteinase-9 activation. The authors therefore propose that these proteins mediate the profibrotic effect of iNOS. Sarit Anavi, Michal Eisenberg-Bord, Michal Hahn-Obercyger, Olga Genin, Mark Pines and Oren Tirosh 2015 95: 914-924; advance online publication, June 22, 2015; 10.1038/labinvest.2015.67 Abstract | Full Text Fibrin supports human fetal islet-epithelial cell differentiation via p70s6k and promotes vascular formation during transplantation In order to increase the yield of β-cells that can be generated for islet transplantation as a treatment for diabetes, the authors examined the factors that regulate pancreatic development and islet cell differentiation. This study shows that fibrin supports human fetal islet epithelial cell differentiation via the mTOR pathway, which is associated with increases in integrin 7alpha;Vβ3 expression. Fibrin also improves graft vascularization when human fetal islet epithelial cells are transplanted subcutaneously, indicating that fibrin can be used to support islet transplantation. Matthew Riopel, Jinming Li, Mark Trinder, George F Fellows and Rennian Wang 2015 95: 925-936; advance online publication, June 1, 2015; 10.1038/labinvest.2015.74 Abstract | Full Text BREAST, SKIN, SOFT TISSUE AND BONE Epstein–Barr virus BZLF1 protein impairs accumulation of host DNA damage proteins at damage sites in response to DNA damage The Epstein-Barr virus (EBV) immediate-early protein BZLF1 is a key mediator in the switch of EBV infection from the latent to the lytic form. In this study, expression of BZLF1 is shown to impair DNA damage response pathways in host cells by blocking the recruitment of 53BP1, a regulator of DNA repair. BZLF1 may function as a link between lytic EBV infection and faulty DNA repair, thus contributing to the carcinogenesis of EBV-associated human epithelial malignancies. Jie Yang, Wen Deng, Pok M Hau, Jia Liu, Victoria M Y Lau, Annie L M Cheung, Michael S Y Huen and Sai W Tsao 2015 95: 937-950; advance online publication, June 1, 2015; 10.1038/labinvest.2015.69 Abstract | Full Text The hepatocyte growth factor receptor as a potential therapeutic target for dedifferentiated liposarcoma Dedifferentiated liposarcomas (DDLPS) are highly resistant to conventional chemo- and radiotherapies. The authors show that stimulation of DDLPS cells with hepatocyte growth factor (HGF) elevates the degree of phosphatidyl-inositol-3-kinase PI3K-AKT and MAP kinase pathway signaling, and that pro-tumorigenic phenotypes such as cell proliferation, invasion, and migration, are significantly enhanced. Met knockdown decreases HGF-induced Met signaling, the invasive and migratory nature of DDLPS cells, and the tumorigenicity of DDLPS cells. Met thus appears to be a promising therapeutic target for treatment of DDLPS. Kate Lynn J Bill, Jeannine Garnett, Xiaoyan Ma, Caitlin D May, Svetlana Bolshakov, Alexander J Lazar, Dina C Lev and Raphael E Pollock 2015 95: 951-961; advance online publication, June 1, 2015; 10.1038/labinvest.2015.62 Abstract | Full Text GENITOURINARY AND REPRODUCTIVE SYSTEMS Transcriptional upregulation of HNF-1β by NF-κB in ovarian clear cell carcinoma modulates susceptibility to apoptosis through alteration in bcl-2 expression Hepatocyte nuclear factor-1 β (HNF-1 β) is a transcriptional factor that modulates cell kinetics and glucose metabolism. However, the molecular mechanisms that govern its regulation and function ovarian clear cell carcinoma (OCCC) have not been elucidated. In this paper, the authors show that HNF-1β/NF-κB signaling may enhance cell survival in OCCC by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2. Erina Suzuki, Sabine Kajita, Hiroyuki Takahashi, Toshihide Matsumoto, Tomoko Tsuruta and Makoto Saegusa 2015 95: 962-972; advance online publication, June 1, 2015; 10.1038/labinvest.2015.73 Abstract | Full Text Please note that you need to be a subscriber or site-licence holder to enjoy full-text access to Laboratory Investigation. In order to do so, please purchase a subscription. You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/nams/svc/myaccount (You will need to log in to be recognised as a nature.com registrant). For further technical assistance, please contact our registration department. For print subscription enquiries, please contact our subscription department. For other enquiries, please contact our customer feedback department. 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