scholarly journals Palmitate and Fructose Interact to Induce Human Hepatocytes to Produce Pro-Fibrotic Transcriptional Responses in Hepatic Stellate Cells Exposed to Conditioned Media

2020 ◽  
Vol 54 (5) ◽  
pp. 1068-1082

BACKGROUND/AIMS: Excessive consumption of dietary fat and sugar is associated with an elevated risk of nonalcoholic fatty liver disease (NAFLD). Hepatocytes exposed to saturated fat or sugar exert effects on nearby hepatic stellate cells (HSCs); however, the mechanisms by which this occurs are poorly understood. We sought to determine whether paracrine effects of hepatocytes exposed to palmitate and fructose produced profibrotic transcriptional responses in HSCs. METHODS: We performed expression profiling of mRNA and lncRNA from HSCs treated with conditioned media (CM) from human hepatocytes treated with palmitate (P), fructose (F), or both (PF). RESULTS: In HSCs exposed to CM from palmitate-treated hepatocytes, we identified 374 mRNAs and 607 lncRNAs showing significant differential expression (log2 foldchange ≥ |1|; FDR ≤0.05) compared to control cells. In HSCs exposed to CM from PF-treated hepatocytes, the number of differentially expressed genes was much higher (1198 mRNAs and 3348 lncRNAs); however, CM from fructose-treated hepatocytes elicited no significant changes in gene expression. Pathway analysis of differentially expressed genes showed enrichment for hepatic fibrosis and hepatic stellate cell activation in P- (FDR =1.30E-04) and PF-(FDR =9.24E-06)
groups. We observed 71 lncRNA/nearby mRNA pairs showing differential expression under PF conditions. There were 90 mRNAs and 264 lncRNAs strongly correlated between the PF group and differentially expressed transcripts from a comparison of activated and quiescent HSCs, suggesting that some of the transcriptomic changes occurring in response to PF overlap with HSC activation. CONCLUSION: The results reported here have implications for dietary modifications in the prevention and treatment of NAFLD.

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Renwei Huang ◽  
Qunwen Pan ◽  
Xiaotang Ma ◽  
Yan Wang ◽  
Yaolong Liang ◽  
...  

Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of transcripts overlapping NDUFA13 and YJEFN3 genes in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of pseudogene 3 of the bromodomain containing 7 molecule, Brd7p3, in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of Wdr47 in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of Cdx2 in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of Meaf6 in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2020 ◽  
Author(s):  
Shahan Mamoor

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of Bcl3 in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.


2009 ◽  
Vol 47 (01) ◽  
Author(s):  
I Strack ◽  
M Scheffler ◽  
S Schievenbusch ◽  
J Riemer ◽  
A Noetel ◽  
...  

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