scholarly journals Rat Hepatocytes Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Liver Regeneration after Partial Hepatectomy

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94868 ◽  
Author(s):  
Yun Zhou ◽  
Jiucheng Xu ◽  
Yunqing Liu ◽  
Juntao Li ◽  
Cuifang Chang ◽  
...  
2010 ◽  
Vol 299 (4) ◽  
pp. G887-G897 ◽  
Author(s):  
Rui E. Castro ◽  
Duarte M. S. Ferreira ◽  
Xiaoxiao Zhang ◽  
Pedro M. Borralho ◽  
Aaron L. Sarver ◽  
...  

New gene regulation study tools such as microRNA (miRNA or miR) analysis may provide unique insights into the remarkable ability of the liver to regenerate. In addition, we have previously shown that ursodeoxycholic acid (UDCA) modulates mRNA levels during liver regeneration. Bile acids are also homeotrophic sensors of functional hepatic capacity. The present study was designed to determine whether miRNAs are modulated in rats following 70% partial hepatectomy (PH) and elucidate the role of UDCA in regulating miRNA expression during liver regeneration (LR). Total RNA was isolated from livers harvested at 3–72 h following 70% PH or sham operations, from both 0.4% (wt/wt) UDCA and control diet-fed animals. By using a custom microarray platform we found that several miRNAs are significantly altered after PH by >1.5-fold, including some previously described as modulators of cell proliferation, differentiation, and death. In particular, expression of miR-21 was increased after PH. Functional modulation of miR-21 in primary rat hepatocytes increased cell proliferation and viability. Importantly, UDCA was a strong inducer of miR-21 both during LR and in cultured HepG2 cells. In fact, UDCA feeding appeared to induce a sustained increase of proliferative miRNAs observed at early time points after PH. In conclusion, miRNAs, in particular miR-21, may play a significant role in modulating proliferation and cell cycle progression genes after PH. miR-21 is additionally induced by UDCA in both regenerating rat liver and in vitro, which may represent a new mechanism behind UDCA biological functions.


2018 ◽  
Vol 59 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Anne Andert ◽  
Hamid P. Alizai ◽  
Tom Florian Ulmer ◽  
Christoph Heidenhain ◽  
Patrick Ziegler ◽  
...  

Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p < 0.0001), and IL-6 (p < 0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: > 122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (< 122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration.


2020 ◽  
Vol 8 (21) ◽  
pp. 1348-1348
Author(s):  
Zetao Ma ◽  
Zhida Shen ◽  
Yingchao Gong ◽  
Jiaqi Zhou ◽  
Xiaoou Chen ◽  
...  

1995 ◽  
Vol 195 (1) ◽  
pp. 201-208 ◽  
Author(s):  
Tsann-Long Hwang ◽  
Hon-Chung Yu ◽  
Pu-Cheng Chen ◽  
Miin-Fu Chen

FEBS Open Bio ◽  
2021 ◽  
Author(s):  
Chun Li ◽  
Bangming Pu ◽  
Long Gu ◽  
Mingwei Zhang ◽  
Hongping Shen ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chuxiang Lei ◽  
Dan Yang ◽  
Wenlin Chen ◽  
Haoxuan Kan ◽  
Fang Xu ◽  
...  

Abstract Background Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks. Methods We analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm. Results We identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells. Conclusion Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.


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