Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage

Abstract

Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.

Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury

“…Moreover, miR-122 levels were elevated in models of nanoparticle and drug-induced liver injury [8,9]. Notably these results remained unchanged when instead of mice rats were analysed [10] and even reflected inter-strain differences in disease severity between different strains of mice [11] By translating these results into the human setting, it became apparent that median levels of miR-122 were significantly up-regulated in HCV-infected patients as well as in drug-induced liver injury when compared with healthy controls [12,13] Moreover, elevated miR-122 serum levels were found in patients after liver transplantation (LTX) when an acute rejection occurred [14].…”

“…Notably these results remained unchanged when instead of mice rats were analysed [10] and even reflected inter-strain differences in disease severity between different strains of mice [11] By translating these results into the human setting, it became apparent that median levels of miR-122 were significantly up-regulated in HCV-infected patients as well as in drug-induced liver injury when compared with healthy controls [12,13] Moreover, elevated miR-122 serum levels were found in patients after liver transplantation (LTX) when an acute rejection occurred [14]. Besides miR-122, several other miRNAs, including miR-29a/b/c, miR-15a, miR-130a, miR-146a, miR-194 and miR-192 were suggested as serum-based markers for acute liver injury [8,9,[12][13][14][15]. ) is ubiquitously expressed in liver, colon, kidney and small intestine [16].…”

Nanomedicine and epigenome. Possible health risks

“…They identified 32 differentially methylated regions including hypermethylation of CREB3L1 and BCL2 genes, associated with mitochondrial-mediated apoptosis via the PI3K/Akt signalling pathway (Zou et al, 2016). Nagano and colleagues reported changes in miR-122 expression as a biomarker of liver damage in mice, induced by exposure to SiNPs of 70 nm diameter (Nagano et al, 2013).…”

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

“…53,54) Precisely predicting the biological effects of nanoparticles is difficult because they induce a wide variety of biological effects; therefore, we are also trying to develop biomarkers not only for proteins but also for bio-derived molecules such as microRNA. 55) Eventually, we hope to develop a battery of biomarkers that can be used to comprehensively screen nanoparticles for safety concerns during the early stages of development.…”