scholarly journals Discrimination between Signaling Pathways in Regulation of Specific Gene Expression by Insulin and Growth Hormone in Hepatocytes

Endocrinology ◽  
2002 ◽  
Vol 143 (10) ◽  
pp. 3766-3772 ◽  
Author(s):  
Pascale Ribaux ◽  
Asllan Gjinovci ◽  
Henry B. Sadowski ◽  
Patrick B. Iynedjian
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Signaling Pathways ◽  
Specific Gene ◽  
Specific Gene Expression

scholarly journals Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1579
Author(s):  
Cankut Çubuk ◽  
Fatma E. Can ◽  
María Peña-Chilet ◽  
Joaquín Dopazo
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Drug Action ◽  
Specific Gene ◽  
Mechanistic Models ◽  
Modeling Framework ◽  
Specific Gene Expression ◽  
Action Mechanisms ◽  
Gender Specific Differences ◽  
Gender Specific

Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-specific gene expression activities have over cell functionality and fate. Moreover, we also used the mechanistic modeling framework to simulate the drug interventions and unravel how drug action mechanisms are affected by gender-specific differential gene expression. Interestingly, some cancers have many biological processes significantly affected by these gender-specific differences (e.g., bladder or head and neck carcinomas), while others (e.g., glioblastoma or rectum cancer) are almost insensitive to them. We found that many of these gender-specific differences affect cancer-specific pathways or in physiological signaling pathways, also involved in cancer origin and development. Finally, mechanistic models have the potential to be used for finding alternative therapeutic interventions on the pathways targeted by the drug, which lead to similar results compensating the downstream consequences of gender-specific differences in gene expression.

scholarly journals Single-cell RNA Sequencing Reveals Transcriptional Signatures and Cell-cell Crosstalk in Patients With Hypertensive Nephropathy

2021 ◽  
Author(s):  
Rong Tang ◽  
Wei Lin ◽  
Chanjuan Shen ◽  
Ting Meng ◽  
Joshua D Ooi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Rna Sequencing ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Distinct Cell ◽  
Single Cell Rna Sequencing ◽  
Cell Crosstalk ◽  
Cell Cell

Abstract BackgroundHypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease, yet the precise mechanisms and cell-specific gene expression changes are still unknown. This study used single-cell RNA sequencing (scRNA-seq) to explore novel molecular mechanisms and gene targets for HTN for the first time. Methods: The gene expression profiles of renal biopsy samples obtained from HTN patients and healthy living donor controls were determined by scRNA-seq technology. Distinct cell clusters, differential gene expression, cell-cell interaction and potential signaling pathways involved in HTN were determined. Results18 distinct cell clusters were identified in kidney from HTN and control subjects. Endothelial cells overexpressed LRG1 , a pleiotropic factor linked to apoptosis and inflammation, providing a potential novel molecular target. HTN endothelium also overexpressed genes linked to cellular adhesion, extracellular matrix accumulation and inflammation. In HTN patients, mesangial cells highly expressed proliferation related signatures ( MGST1 , TMSB10, EPS8 and IER2 ) not detected in renal diseases before. The upregulated genes in tubules of HTN were mainly participating in inflammatory signatures including IFN-γ signature, IL-17 signaling and TLR signaling. Specific gene expression of kidney-resident CD8 + T cells exhibited a proinflammatory, chemotactic and cytotoxic phenotype. Furthermore, receptor-ligand interaction analysis indicated cell-cell crosstalk in kidney contributes to recruitment and infiltration of inflammatory cells into kidneys, and fibrotic process in hypertensive renal injury. ConclusionsIn summary, our data identifies a distinct cell-specific gene expression profile, pathogenic signaling pathways and potential cell-cell communications in the pathogenesis of HTN. These findings will provide a promising novel landscape for mechanisms and treatment of HTN.

scholarly journals Growth hormone mediates zone-specific gene expression in liver

FEBS Letters ◽  
1993 ◽  
Vol 327 (2) ◽  
pp. 237-240 ◽  
Author(s):  
T. Oinonen ◽  
E. Nikkola ◽  
K.O. Lindros
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Specific Gene ◽  
Specific Gene Expression
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