RGD Reference Report - MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats. - Rat Genome Database

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MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats.

Authors: Wang, Xin-Yong  Zhang, Xian-Zhao  Li, Feng  Ji, Qing-Rong 
Citation: Wang XY, etal., J Cell Physiol. 2019 Apr;234(4):4997-5010. doi: 10.1002/jcp.27300. Epub 2018 Oct 20.
RGD ID: 243065124
Pubmed: PMID:30341898   (View Abstract at PubMed)
DOI: DOI:10.1002/jcp.27300   (Journal Full-text)

Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR-128-3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet β-cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR-128-3p, ISL1, and the Wnt signaling pathway- and apoptosis-related genes. Finally, apoptosis of islet β-cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet β-cell function were decreased. Furthermore, upregulation of miR-128-3p and ISL1 gene silencing promoted the expression of Wnt-1, β-catenin, GSK-3β, and Bax and the phosphorylation of β-catenin and GSK-3β, inhibited c-fos, PDX-1, and Bcl-2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR-128-3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR-128-3p may serve as a potential target for the treatment of T2DM.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ISL1Humantype 2 diabetes mellitus  ISOIsl1 (Rattus norvegicus)mRNA and protein:decreased expression:pancreas:RGD 
Isl1Rattype 2 diabetes mellitus  IEP mRNA and protein:decreased expression:pancreas:RGD 
Isl1Mousetype 2 diabetes mellitus  ISOIsl1 (Rattus norvegicus)mRNA and protein:decreased expression:pancreas:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Isl1Ratpositive regulation of type B pancreatic cell apoptotic process  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Isl1Ratcytoplasm  IDA MMO:0000538RGD 

Objects Annotated

Genes (Rattus norvegicus)
Isl1  (ISL LIM homeobox 1)

Genes (Mus musculus)
Isl1  (ISL1 transcription factor, LIM/homeodomain)

Genes (Homo sapiens)
ISL1  (ISL LIM homeobox 1)


Additional Information