Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

Tran, Melanie; Lee, Sang‐Min; Shin, Dong‐Ju; Wang, Li

doi:10.1172/jci.insight.96094

Cited by 50 publications

(39 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data were expressed as mean ± SEM and represented by triplicate assays. Statistical analysis was performed using one‐way analysis of variance among multiple groups and the Student t test between two groups . P < 0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers

Jiang

Huang

Cai

et al. 2018

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re‐induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined in situ hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell‐specific markers in the livers of cholestatic mouse models and patients with cholestasis. H19RNA+ cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19)+ cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5‐diethoxycarbony1‐1,4‐dihydrocollidine (DDC), and multidrug‐resistant gene 2 knockout (Mdr2–/–) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens. In contrast, double‐positive H19RNA+/sex‐determining region Y (SRY)‐box 9 (SOX9)+ ductal progenitor cells, H19RNA+/hepatocyte nuclear factor 4α (HNF4α)+ hepatocytes, H19RNA+/F4/80+ Kupffer cells, HNF4α+/SOX9+ hybrid hepatocytes, as well as triple‐positive H19RNA+/HNF4α+/SOX9+ periportal hepatocytes were identified. In addition, H19RNA could not be detected in mesenchymal cell marker desmin+ cells. Furthermore, H19RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells. Conclusion: H19RNA is localized in HNF4α+ periportal hepatocytes, SOX9+ ductal progenitor cells, and F4/80+ Kupffer cells but not in CK19+ cholangiocytes and desmin+ stellate cells in cholestatic livers.

show abstract

Section: Methodsmentioning

confidence: 99%

H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers

Jiang

Huang

Cai

et al. 2018

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

show abstract

“…More studies are needed to explore their mechanisms but some of those have recently been discovered. Examples are the roles of miR-141/200c in diminishing NASH-associated hepatic steatosis and inflammation through reprogramming of lipids and inflammation signaling pathways [24] and of miRNA-21 in decreasing inflammation and fibrosis via the restoration of PPARα expression [25].…”

Section: Factors That Underlie Predisposition To Nafldmentioning

confidence: 99%

Pathogenesis of NASH: the Impact of Multiple Pathways

Noureddin

Sanyal

2018

Curr Hepatology Rep

View full text Add to dashboard Cite

Purpose of review Advancing our understanding of the mechanisms that underlie NASH pathogenesis. Recent findings Recent findings on NASH pathogenesis have expanded our understanding of its complexity including: (1) there are multiple parallel hits that lead to NASH; (2) the microbiota play an important role in pathogenesis, with bacterial species recently shown to accurately differentiate between NAFL and NASH patients; (3) the main drivers of liver cell injury are lipotoxicity caused by free fatty acids (FFAs) and their derivatives combined with mitochondrial dysfunction; (4) decreased endoplasmic reticulum (ER) efficiency with increased demand for protein synthesis/folding/repair results in ER stress, protracted unfolded protein response, and apoptosis; (5) upregulated proteins involved in multiple pathways including JNK, CHOP, PERK, BH3-only proteins, and caspases result in mitochondrial dysfunction and apoptosis; and (6) subtypes of NASH in which these pathophysiological pathways vary may require patient subtype identification to choose effective therapy. Summary Recent pathogenesis studies may lead to important therapeutic advances, already seen in patients treated with ACC, ASK1 and SCD1 inhibitors and FXR agonists. Further advancing our understanding of mechanisms underlying NASH pathogenesis and the complex interplay between them will be crucial for developing effective therapies.

show abstract

“…MiR-200/375 combined with TF Hes1, as hubs (with much connections and degree) regulating 18 genes, played important roles in our network ( Figure 5C ). The previous study reported that miR-200 deficiency diminished hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways ( Tran et al, 2017 ), and therapeutic inhibition of miR-375 can attenuate inflammatory response ( Garikipati et al, 2017 ). Both miR-200 and miR-375 could targ etaldehyde dehydrogenase ( Aldh1b1 ), which may in turn increase ROS and proinflammatory activities ( Toye et al, 2007 ).…”

Section: Resultsmentioning

confidence: 99%

Investigating the Molecular Mechanism of Aqueous Extract of Cyclocarya paliurus on Ameliorating Diabetes by Transcriptome Profiling

Luo

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Diabetes is generally regarded as a metabolic disorder disease caused by various reasons, including pancreas islet injury and lipid metabolism disorders. The aqueous extract of Cyclocarya paliurus leaves (CPAE) was reported to be anti-diabetic. However, the possible molecular mechanisms have not been investigated. To elucidate the anti-diabetic effects of CPAE and the underlying potential mechanisms, we performed transcriptome profiling (RNA-Seq and miRNA-Seq) on the pancreas and liver from non-diabetic, diabetic and diabetic-CPAE rats. Our results demonstrated the CPAE could reduce excessive oxidative stress and inflammation in the pancreas, and maintain the balance of glucose and lipid metabolism in the liver. Transcriptome profiling and regulatory network analysis indicated that CPAE may ameliorate diabetes through improving β-cell survival and strengthening insulin secretion in the pancreas. Meanwhile, CPAE could improve impaired lipid metabolism and reduce excessive oxidative damage in the liver probably through miR-200/375-Aldh1b1/Hps5-Hes1 co-regulatory network. Taken together, our biochemical experiments combined with transcriptome profiling showed that the effects of CPAE on anti-diabetes may work through protecting pancreatic β-cell, improving dyslipidaemia and lipid metabolism disorders.

show abstract

Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

Cited by 50 publications

References 45 publications

H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers

H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers

Pathogenesis of NASH: the Impact of Multiple Pathways

Investigating the Molecular Mechanism of Aqueous Extract of Cyclocarya paliurus on Ameliorating Diabetes by Transcriptome Profiling

Contact Info

Product

Resources

About