title: Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice.
abstract: Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO(2) NP-exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO(2) NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO(2) NPs exposure.
authors.affiliation: Medical College, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Cui
authors.forename: Huiting
authors.initials: H
authors.lastname: Liu
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zengli
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008111:Liver Function Tests; D053768:Metal Nanoparticles; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium