Fan Zhang

// Fan Zhang 1, 2 , Hongsheng Wang 2 , Xianfeng Wang 3 , Guanmin Jiang 4 , Hao Liu 5 , Ge Zhang 2 , Hao Wang 2 , Rui Fang 2 , Xianzhang Bu 2 , Shaohui Cai 6 , Jun Du 2 1 Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, PR China 2 Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China 3 Shijiazhuang City Center for Disease Control and Prevention, Shijiazhuang 050000, PR China 4 Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, PR China 5 Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, PR China 6 Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou 510632, PR China Correspondence to: Jun Du, email: dujun@mail.sysu.edu.cn Shaohui Cai, email: caish5689@sina.com Keywords: SNAIL, TGF-β, macrophage polarization, tumor-associated macrophage, immunotherapy Received: September 24, 2015     Accepted: June 29, 2016     Published: July 13, 2016 ABSTRACT Tumor-associated macrophages (TAMs) are a major component of leukocytic infiltrate in tumors, which facilitates tumor progression and promotes inflammation. TGF-β promotes the differentiation of non-activated macrophages into a TAM-like (M2-like) phenotype; however, the underlying mechanisms are not clear. In this study, we found that TGF-β induces a M2-like phenotype characterized by up-regulation of the anti-inflammatory cytokine IL-10, and down-regulation of the pro-inflammatory cytokines TNF-α and IL-12. In human THP-1 macrophages, overexpression of SNAIL caused M2-like differentiation by inhibiting pro-inflammatory cytokine release and promoting the expression of M2-specific markers. By contrast, SNAIL knockdown promoted M1 polarization through up-regulation of pro-inflammatory cytokines and abolished TGF-β-mediated M2-polarization of THP-1 macrophages. The SMAD2/3 and PI3K/AKT signaling pathways were crucial for TGF-β-induced SNAIL overexpression in THP-1 cells. These findings suggest that TGF-β skews macrophage polarization towards a M2-like phenotype via SNAIL up-regulation, and blockade of TGF-β/SNAIL signaling restores the production of pro-inflammatory cytokines. This study provides new understanding of the role of SNAIL in M2 polarization of macrophages, and suggests a potential therapeutic target for antitumor immunity.

Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis.