miRNA in Rat Liver Sinusoidal Endothelial Cells and Hepatocytes and Application to Circulating Biomarkers that Discern Pathogenesis of Liver Injuries

Oda, Shingo; Takeuchi, Masaki; Akai, Shigeyasu; Shirai, Yuji; Tsuneyama, Koichi; Yokoi, Tsuyoshi

doi:10.1016/j.ajpath.2017.12.007

Cited by 20 publications

(19 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data indicate that miR‐218a‐5p and miR‐143‐3p increased in the plasma of rats upon biliary injury in the early stage, as supported by the findings that miR‐218a‐5p was expressed in cholangiocytes but not in hepatocytes from naïve rats (Figure 4). Unexpectedly, however, miR‐143‐3p was mainly expressed in hepatocytes, resembling hepatocyte‐specific miR‐122‐5p (Oda et al, 2018). It remains unknown why plasma miR‐143‐3p levels increased in cholestatic liver injury but not in hepatocellular liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…A hepatocyte‐specific miR‐122‐5p was identified as a promising biomarker for the early prediction of hepatocellular liver injury (Wang et al, 2009), and numerous subsequent studies have focused on this miRNA. However, despite the fact that each liver cell type shows different miRNA expression patterns (Oda et al, 2018), whether circulating miRNAs from liver cells other than hepatocytes could be biomarkers for liver injury have been scarcely studied. We recently performed an RNA‐sequencing analysis of miRNAs in rat plasma to identify specific biomarkers for detecting hepatocellular injury, cholestasis, and steatosis (Kagawa et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Oda

Hirabuki

Takeuchi

et al. 2021

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

MicroRNAs (miRNA) have received considerable attention as potential biomarkers for drug‐induced liver injury. We recently reported that the plasma levels of miR‐143‐3p and miR‐218a‐5p increased in severe cholestasis in rats. This study aimed to investigate whether these miRNAs increase in a severity‐dependent manner and to elucidate their pathophysiological roles in cholestasis. Male Sprague–Dawley rats were orally administered different doses of α‐naphthylisothiocyanate or 4,4‐methylenedianiline to induce acute cholestasis. They were also orally administered acetaminophen or thioacetamide to induce hepatocellular injury. We found that plasma miR‐143‐3p and miR‐218a‐5p levels increased in a dose‐dependent manner in cholestatic rats but not in hepatocellular injury. Bioinformatic analysis provided putative target genes of hsa‐miR‐218‐5p, rno‐miR‐218a‐5p, and mmu‐miR‐218‐5p, among which GNAI2, PPP1CB, and PPP2R5A were experimentally validated as their direct target genes in human cholangiocyte line MMNK‐1. Proliferation of MMNK‐1 cells was significantly suppressed after overexpression of miR‐218‐5p and transduction of siRNAs for GNAI2, PPP1CB, and PPP2R5A. In the cholestatic livers of rats, Ppp1cb and Ppp2r5a expression levels decreased, whereas Gnai2 expression levels increased compared with those in vehicle‐treated rats, suggesting that Ppp1cb and Ppp2r5a may be under the control of miR‐218a‐5p in vivo. In conclusion, our data suggest that miR‐218(a)‐5p is involved in the suppression of cholangiocyte proliferation by inhibiting the expression of PPP1CB and PPP2R5A, thereby contributing to the pathogenesis of cholestasis; and miR‐218a‐5p leaks into the plasma probably from damaged cholangiocytes in a severity‐dependent manner in rats. Therefore, miR‐218a‐5p overexpression could be one of the underlying mechanisms of acute cholestatic liver injury in rats.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Oda

Hirabuki

Takeuchi

et al. 2021

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

show abstract

“…(27). In a rat model miR-511-3p in plasma was recommended as a possible biomarker for liver sinusoidal endothelial cells damage (28). MiR-122-5p as the most abundant microRNA in the liver plays an important role in biological functions and significance in various diseases (29).…”

Section: Discussionmentioning

confidence: 99%

Importance of miR-125a-5p and miR-122-5p expression in patients with HBV infection

Lak

Yaghobi

Garshasbi

2020

Cell Mol Biol (Noisy-le-grand)

View full text Add to dashboard Cite

MicroRNAs (miRNAs) as a small RNA and post-transcriptional modulator are shown to have regulatory effects for different cellular activities and pathways, such as metabolism, virus replication and also cell growth. In addition, miRNAs can regulate the replication of the hepatitis B virus (HBV). Therefore, the expression profile of miRNAs was evaluated in HBV infected patient groups and healthy controls. The expression levels of following microRNAs (as noninvasive biomarkers) were compared in two experimental (those with various stages of HBV infection) and control groups to evaluate their diagnosis ability: miR-122-5p, miR-125a-5p, miR-199a-3p, miR-210-5p, miR-205-5p, miR-155-5p, miR-372-5p, and miR-1-5p. RNA extraction was performed for 45 serum samples. The miRCURY LNA™ Universal RT-miRNA-PCR system and miRNA PCR panels were used for measuring microRNA expression profiles. To normalize quantitative values, the endogenous reference by UniSp6 expression was used.Serum miR-125a-5p and miR-122-5p were significantly higher in patients in different stages of HBV infection (p<0.001) than in controls (p<0.001). Receiver operating characteristic (ROC) curve analyses suggested that serum miR-125a-5p and miR-122-5p have significant diagnostic value for HBV infection. A significant difference was not found in terms of serum levels of other miRs (miR-199a-3p, miR-210-5p, miR-205-5p, miR-155-5p, miR-372-5p and miR-1-5p). Results suggest that miR-125a-5p and miR-122-5p can be used as possible noninvasive biomarkers for monitoring of HBV infection need to confirm in future completed studies.

show abstract

“…Briefly, miRNA expressed in control or alcohol-fed animal samples were tested against a known set of miRNAs associated with HSCs, rat liver sinusoidal endothelial cells (LSECs), or Kupffer cells (KCs) to determine if these miRNA sets display significant correlation with expression patterns from a particular biological state. These miRNA signatures were derived from previously published miRNA profiling data from primary rat hepatic stellate cells activated in culture (21), rat liver sinusoidal endothelial cells (LSECs) compared with other liver cell types (22), and mouse Kupffer cells (KCs) at 3 days after 70% PHx (23). The HSC signature consisted of 16 upregulated miRNAs and 26 downregulated miRNAs.…”

Section: Gene Set Enrichment Analysismentioning

confidence: 99%

Dysregulation of miR-21-associated miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration

Parrish

Srivastava

Juskeviciute

et al. 2021

Physiological Genomics

View full text Add to dashboard Cite

Impaired liver regeneration has been considered as a hallmark of progression of alcohol-associated liver disease. Our previous studies demonstrated that in vivo inhibition of the microRNA (miRNA) miR21 can restore regenerative capacity of the liver in chronic ethanol-fed animals. The present study focuses on the role of microRNA regulatory networks that are likely to mediate the miR-21 action. Rats were chronically fed an ethanol-enriched diet along with pair-fed control animals and treated with AM21 (anti-miR-21), a locked nucleic acid antisense to miR-21. Partial hepatectomy (PHx) was performed and miRNA expression profiling over the course of liver regeneration was assessed. Our results showed dynamic expression changes in several miRNAs post PHx, notably with altered miRNA expression profiles between ethanol versus control groups. We found that in vivo inhibition of miR-21 led to correlated differential expression of miR-340-5p, and anti-correlated expression of miR-365, let-7a, miR-1224 and miR-146a across all sample groups post PHx. Gene set enrichment analysis identified a miRNA signature significantly associated with hepatic stellate cell activation within whole-liver tissue data. We hypothesized that at least part of the PHx-induced miRNA network changes responsive to miR-21 inhibition is localized to hepatic stellate cells. We validated this hypothesis using AM21 and TGF-β treatments in LX-2 human hepatic stellate cells in culture, and measured expression levels of select miRNAs by quantitative RT-PCR. Based on the in vivo and in vitro results, we propose a hepatic stellate cell miRNA regulatory network as contributing to the restoration of liver regenerative capacity by miR-21 inhibition.

show abstract

miRNA in Rat Liver Sinusoidal Endothelial Cells and Hepatocytes and Application to Circulating Biomarkers that Discern Pathogenesis of Liver Injuries

Cited by 20 publications

References 38 publications

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Importance of miR-125a-5p and miR-122-5p expression in patients with HBV infection

Dysregulation of miR-21-associated miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration

Contact Info

Product

Resources

About