ABSTRACT
Interleukin (IL)-33/ST2 pathway plays a pivotal role in tumorigenesis through influencing cancer stemness, tumor growth, metastasis, angiogenesis, and accumulation of regulatory T cells in tumor microenvironments. The aim of this study was to investigate the association of IL-33 rs7025417 and ST2 rs3821204 with the risk of hepatocellular carcinoma (HCC). Genotyping of IL-33 rs7025417 and ST2 rs3821204 was carried out using a Taqman assay. IL-33 and ST2 mRNA was examined using real-time PCR and plasma IL-33 and sST2 levels were measured using enzyme-linked immunosorbent assay. The ST2 rs3821204 CC genotype was associated with a significantly increased risk of HCC (CC vs. GG: adjusted ORâ¯=â¯2.29, 95% CI, 1.39-3.78; dominant model: adjusted ORâ¯=â¯1.58, 95% CI, 1.12-2.23; recessive model: adjusted ORâ¯=â¯1.88, 95% CI, 1.21-2.93; C vs. G: adjusted ORâ¯=â¯1.53, 95% CI, 1.20-1.95). Gene-environment interaction analysis showed that the risk effect of rs3821204 CG/CC genotypes was more evident in smokers (adjusted ORâ¯=â¯1.70, 95% CI, 1.13-2.55) and drinkers (adjusted ORâ¯=â¯1.57, 95% CI, 1.04-2.37). The increased risk was also observed in combined analysis. Moreover, HCC patients with ST2 rs3821204 CC genotype had higher levels of mRNA and protein expression (Pâ¯<â¯0.05). These findings suggest that ST2 rs3821204 CC genotype may contribute to hepatocarcinogenesis by enhancing ST2 production at the transcriptional and translational level.
Subject(s)
Asian People/genetics , Carcinoma, Hepatocellular/genetics , Genetic Predisposition to Disease/genetics , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/genetics , Liver Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Alleles , Case-Control Studies , Female , Gene Frequency/genetics , Genetic Association Studies/methods , Genotype , Humans , Male , Middle Aged , Signal Transduction/genetics , Tumor Microenvironment/geneticsABSTRACT
Fat flap transplantation is frequently performed in patients suffering from soft tissue defects resulting from disease or trauma. This study explored the feasibility of constructing vascularized fat flaps using rabbit adipose-derived stem cells (rASCs) and collagen scaffolds in a rabbit model. We evaluated rASCs proliferation, paracrine function, adipogenesis, vascularization, and CD54 expression, with or without HIF-1α transfection in vitro and in vivo. We observed that adipogenic differentiation potential was greater in rASCs with high CD54 expression (CD54+rASCs) than in those with low expression (CD54-rASCs), both in vitro and in vivo. HIF-1α overexpression not only augmented this effect, but also enhanced cell proliferation and paracrine function in vitro. We also demonstrated that HIF-1α-transfected CD54+rASCs showed enhanced paracrine function and adipogenic capacity, and that paracrine function increases expression of angiogenesis-related markers. Thus, CD54+rASCs overexpressing HIF-1α enhanced large volume vascularized fat flap regeneration in rabbits, suggesting CD54 may be an ideal candidate marker for ASCs adipogenic differentiation.