scholarly journals A Transcriptional Sequencing Analysis of Islet Stellate Cell and Pancreatic Stellate Cell

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaohang Wang ◽  
Wei Li ◽  
Juan Chen ◽  
Sheng Zhao ◽  
Shanhu Qiu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Differentially Expressed Genes ◽  
Stellate Cell ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Sequencing Analysis ◽  
Pancreatic Stellate Cell ◽  
Genome Wide ◽  
Differential Expressed Genes

Background. Our previous studies have shown that islet stellate cell (ISC), similar to pancreatic stellate cell (PSC) in phenotype and biological characters, may be responsible for the islet fibrosis in type 2 diabetes. To further identify the differences between PSC and ISC and for better understanding of the physiological function of ISC, we employed genome-wide transcriptional analysis on the PSCs and ISCs of Wistar rats. Method. PSCs and ISCs from each rat were primarily cultured at the same condition. Genome-wide transcriptional sequence of stellate cells was generated. The identified differentially expressed genes were validated using RT-PCR. Results. 32 significant differentially expressed genes between PSCs and ISCs were identified. Moreover, collagen type 11a1 (COL11A1), was found to be expressed 2.91-fold higher in ISCs compared with PSCs, indicating that COL11A1 might be a potential key gene modulating the differences between PSC and ISC. Conclusions. Our study identified and validated the differences between PSC and ISC in genome-wide transcriptional scale, confirming the assumption that ISC and PSC are similar other than identical. Moreover, our data might be instrumental for further investigation of ISC and islet fibrosis, and some differential expressed genes may provide an insight into new therapeutic targets for type 2 diabetes.

scholarly journals Identification of Potential Therapeutic Targets in the Liver of Pioglitazone-Treated Type 2 Diabetes Sprague-Dawley Rats via Expression Profile Chip and iTRAQ Assay

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Zhong-Xia Lu ◽  
Wen-Jun Xu ◽  
Yang-Sheng Wu ◽  
Chang-Yu Li ◽  
Yi-Tao Chen
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Differentially Expressed Genes ◽  
Fasting Blood Glucose ◽  
Treated Group ◽  
Differentially Expressed ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.

scholarly journals Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus

2020 ◽  
Vol 10 (1) ◽  
pp. 85
Author(s):  
Enrique Almanza-Aguilera ◽  
Álvaro Hernáez ◽  
Dolores Corella ◽  
Albert Sanllorente ◽  
Emilio Ros ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Log P ◽  
P Value ◽  
Z Score ◽  
Elderly Individuals ◽  
Cancer Signaling

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini–Hochberg-adjusted p-value were >1.30 and their absolute z-scores were >2.0 (≥2.0 meant “upregulation” and ≤ −2.0 “downregulation”). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, −log(p-value) = 32.3; 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, −log(p-value) = 2.03) and paxillin (z-score = 2.33, −log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = −2.14, −log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

scholarly journals Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment

2020 ◽  
Author(s):  
Shatovisha Dey ◽  
Sheng Liu ◽  
Tricia D Factora ◽  
Solaema Taleb ◽  
Primavera Riverahernandez ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Stellate Cell ◽  
Critical Role ◽  
Differentially Expressed ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Stellate Cell ◽  
Western Blots ◽  
Incidence And Mortality

Abstract BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression. MethodsIn this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing hPSC cells and controls. Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top candidate miR-29a targets in hPSC cells transfected with miR-29a mimic or scramble control. ResultsRNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis. ConclusionsTogether, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-tumor cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies.

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