Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats

Saruwatari, Junji; Dong, Chao; Utsumi, Teruo; Tanaka, Masanori; McConnell, Matthew; Iwakiri, Yasuko

doi:10.1038/s41598-018-36297-0

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…However, significant congestion was not observed in the intestine, kidney, and spleen in pIVCL mice (Figure S2a-c). To assess the effect of congestion in other organs, it is preferable to use intrahepatic IVC ligation for renal congestion or partial PV ligation model 16 for intestinal and splenic congestion. Further confirmational study is needed to investigate the impact of chronic congestion not only on the liver but also on other organs by using clinical samples.…”

Section: Discussionmentioning

confidence: 99%

Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy

Kawai

Osawa

Tsunoda³

et al. 2022

Hepatology Research

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Aim Congestive hepatopathy often leads to liver fibrosis and hepatocellular carcinoma. Imaging modalities provided clinical evidence that elevation of liver stiffness and tumor occurrence are mainly induced in the periphery of the liver in patients with congestive hepatopathy. However, clinical relevance of liver stiffness and liver fibrosis is unclear because liver congestion itself increases liver stiffness in congestive hepatopathy. It also unclear which factors configure such regional disparity of tumor development in patients with congestive hepatopathy. To answer these questions, we evaluated the macroscopic spatial distribution of liver fibrosis and tumors in the murine model of congestive hepatopathy. Methods Chronic liver congestion was induced by partial ligation of the suprahepatic inferior vena cava. Distribution of liver congestion, fibrosis, and tumors in partial ligation of the suprahepatic inferior vena cava mice were assessed by histological findings, laser microdissection (LMD)‐based qPCR and enhanced computed tomography. LMD‐based RNA‐sequencing was performed to identify causal factors that promote tumor development in congestive hepatopathy. Results Liver fibrosis was mainly induced in the periphery of the liver and co‐localized with distribution of liver congestion. Liver tumors were also induced in the periphery of the liver where liver congestion and fibrosis occurred. LMD‐based RNA‐sequencing revealed the upregulation of extracellular matrix/collagen fibril‐, wound healing‐, angiogenesis‐, morphogenesis‐, and cell motility‐related signaling pathways in periphery of liver compared with liver center. Conclusions Our findings showed the experimental relevance of liver congestion, fibrosis, and tumor development in congestive hepatopathy, and may provide important locational information. Macroscopic regional disparity observed in this murine model should be considered to manage patients with congestive hepatopathy.

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Section: Discussionmentioning

confidence: 99%

Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy

Kawai

Osawa

Tsunoda³

et al. 2022

Hepatology Research

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“…Target prediction and functional annotation of miRNAs were performed using a previously reported procedure 34 . Target genes for differentially expressed miRNAs were identified using miRGate ( http://mirgate.bioinfo.cnio.es/miRGate/ ), which processes data using 5 computational tools (miRanda, RNAhybrid, Pita, MicroTar and TargetScan) 35 .…”

Section: Methodsmentioning

confidence: 99%

The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells

Takahashi

Saruwatari

Fujimoto

et al. 2021

Sci Rep

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Trabecular meshwork (TM) and Schlemm’s canal (SC) are the main structures within the conventional outflow pathway, and TM cells and SC endothelial (SCE) cells are essential for controlling intraocular pressure. To examine the interaction between TM cells and SCE cells, we investigated whether exosomes contribute to intercellular communication. Additionally, TM cells in glaucoma acquire mesenchymal characteristics in response to transforming growth factor (TGF)-β2 and extracellular matrix proteins such as collagen type 1 (Col-1); these changes result in increased resistance of aqueous outflow. In this study, we stimulated TM cells with TGF-β2 and Col-1 and characterized the exosomal miRNAs (exomiRs) released in response to each stimulus. Isolated exosomes were rich in miRNAs, with downregulated miR-23a-5p and upregulated miR-3942-5p and miR-7515 levels following Col-1 or TGF-β2 stimulation. Next, a miRNA-mRNA network under TGF-β2 stimulation was constructed. There were no connections among the 3 miRNAs and predicted genes under Col-1 stimulation. GO and KEGG analyses revealed that the identified miRNAs were associated with various signaling pathways, including the inflammatory response. Interestingly, SCE cells treated with miR-7515 mimic showed increased VEGFA, VEGFR2, PECAM, and Tie2 expression. Ultrastructures typical of exosomes and positive staining for exosomal markers were observed in human TM cells. Our data showed that TM cells may communicate with SCE cells via exomiRs and that miR-7515 may be important for SCE cell reprogramming.

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“…The impact of miRNAs on hepatic stellate cells and other signaling pathways in cirrhosis has been reviewed in-depth [ 28 – 31 ], whereas the molecular role of miRNAs in hypersplenism has only been recently described. Whole-genome microarray analysis has identified a distinct miRNAome in the enlarged spleens of animals with partial portal vein ligation-induced hypertension, including twenty-two downregulated miRNAs that would normally suppress fibrotic related mRNAs (e.g., Col1a1 , Serpine1 ) [ 32 •]. Intriguingly, miRNA-615-3p was found to be highly expressed in the splenic macrophages of cirrhosis-related portal hypertensive patients who underwent splenectomy [ 33 ].…”

Section: Micrornas In the Gut-liver Axismentioning

confidence: 99%

Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis

et al. 2021

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Purpose of Review To review the current knowledge on interactions between dietary factors and microRNAs (miRNAs) in essential hypertension (EH) pathogenesis. Recent Findings There exists an integration of maintenance signals generated by genetic, epigenetic, immune, and environmental (e.g., dietary) factors that work to sustain balance in the gut-liver axis. It is well established that an imbalance in this complex, intertwined system substantially increases the risk for EH. As such, pertinent research has been taken to decipher how each signal operates in isolation and together in EH progression. Recent literature indicates that both macro- and micronutrients interrupt regulatory miRNA expressions and thus, alter multiple cellular processes that contribute to EH and its comorbidities. We highlight how carbohydrates, lipids, proteins, salt, and potassium modify miRNA signatures during EH. The disruption in miRNA expression can negatively impact communication systems such as over activating the renin-angiotensin-aldosterone system, modulating the vascular smooth muscle cell phenotype, and promoting angiogenesis to favor EH. We also delineate the prognostic value of miRNAs in EH and discuss the pros and cons of surgical vs dietary prophylactic approaches in EH prevention. Summary We propose that dietary-dependent perturbation of the miRNA profile is one mechanism within the gut-liver axis that dictates EH development.

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Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats

Cited by 4 publications

References 56 publications

Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy

Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy

The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells

Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis

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