RGD Reference Report - Aldosterone and TGF-beta(1) synergistically increase PAI-1 expression in hepatic stellate cells of rats. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Aldosterone and TGF-beta(1) synergistically increase PAI-1 expression in hepatic stellate cells of rats.

Authors: Wang, SL  Wu, HM  He, CZ  Yang, L  Gao, HJ  Yang, CQ 
Citation: Wang SL, etal., Int J Clin Exp Pathol. 2015 Sep 1;8(9):9845-53. eCollection 2015.
RGD ID: 11073721
Pubmed: PMID:26617694   (View Abstract at PubMed)
PMCID: PMC4637779   (View Article at PubMed Central)

OBJECTIVE: Aldosterone is related to the fibrosis of several organs, but the specific mechanism underlying the aldosterone induced hepatic fibrosis is still unclear. METHODS: Separation, culture and identification of primary hepatic stellate cells (HSCs): The fluids and digestives used in the present study were able to completely remove blood cells, digest hepatocytes and matrix, and effectively separate HSCs. The in situ perfusion was performed at 2 steps: in situ perfusion with pre-perfusion fluid and ex vivo perfusion with enzyme-containing perfusion fluid. Influence of Ald on PAI-1 and Smad expressions in HSCs: cells were divided into control group, Ald group (10(-6) M), spironolactone (SPI) group and Ald+SPI group, and the mRNA and protein expressions of PAI-1 and Smad were detected. Ald induced type I collagen expression in HSCs: Immunohistochemistry was performed to detect type I collagen expression in the supernatant of control group, Ald group (10(-6) M), TGF-beta1 group, and Ald+TGF-beta1 group. Influence of Ald and TGF-beta1 on PAI-1 expression in HSCs: cells were divided into control group, Ald group (10(-6) M), TGF-beta1 group, and Ald+TGF-beta1 group, and the mRNA and protein expressions of PAI-1 were determined by RT-PCR and Western blot assay, respectively. Synergistic effect of Ald and TGF-beta1 on PAI-1 expression in HSCs: cells were divided into control group, Ald group (10(-6)), TGF-beta1 group, Ald (10(-6) M)+TGF-beta1 group, Ald (10(-7) M)+TGF-beta1 group and Ald (10(-8) M)+TGF-beta1 group, and the mRNA and protein expressions of PAI-1 were detected by RT-PCR and Western blot assay, respectively. RESULTS: The survival rate, purity, markers and activation of HSCs were determined after separation. Influence of Ald on PAI-1 expression in HSCs: PAI-1 expression increased in HSCs of Ald group, SPI group and Ald+API group, and the PAI-1 expression in Ald group and Ald+SPI group was significantly higher than in control group (P<0.01). Influence of Ald on Smad expression in HSCs: Smad expression in Ald group, TGF-beta1 group and ALD+TGF-beta1 group was markedly higher than in control group (P<0.05). Smad expression in ALD+TGF-beta1 group increased significantly when compared with Ald group (P<0.01). Ald induced type I collagen expression in HSCs: type I collagen expression in Ald group, TGF-beta1 group and ALd+TGF-beta1 group was dramatically higher than in control group (P<0.05), and it in ALd+TGF-beta1 group was also significantly different from that in Ald group and TGF-beta1 group (P<0.01). Synergistic effects of Ald and TGF-beta1 on PAI expression in HSCs: PAI-1 expression in treated cells was markedly higher than in control group (P<0.01). PAI-1 expression in 10(-6) M Ald+5 ng/ml TGF-beta1 group increased dramatically as compared to Ald group and TGF-beta1 group (P<0.01), but the increased PAI-1 expression reduced after SPI treatment. Ald at different concentrations exerts synergistic effect with TGF-beta1 to increase PAI-1 expression in HSCs: PAI-1 expression in HSCs after different treatments increased markedly as compared to control group (P<0.01). Significant difference in PAI-1 expression was observed in 10(-6) M Ald+50 pg/ml TGF-beta1 group and 10(-6) M Ald group (P<0.01), PAI-1 expression in 10(-7) M Ald+50 pg/ml TGF-beta1 group was significantly higher than in 50 pg/ml TGF-beta1 group (P<0.01), but the PAI-1 expression in 10(-7) M Ald+50 pg/ml TGF-beta1 group was similar to that in 10(-6) M Ald group (P>0.05). CONCLUSION: Aldosterone is able to activate HSCs and increase PAI-1 expression during hepatic fibrosis, which may be inhibited by spironolactone. Aldosterone and TGF-beta1 may synergistically act on HSCs to increase PAI-1 expression as compared to treatment with aldosterone or TGF-beta1 alone. Aldosterone or TGF-beta1 alone may slightly increase PAI-1 expression in HSCs, which can be inhibited by spironolactone.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to aldosterone  IEP 11073721 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)


Additional Information