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Updated: Jun 25, 2025
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Combining experiments and bioinformatics to identify transforming growth factor-β1 as a key regulator in angiotensin
Wenni Zhang1, Shuangming Cai1, Fei Wu2
1Medical Intensive Care Unit, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China.
Introduction:
Accelerated senescence of trophoblast may cause several diverse pregnancy outcomes; however, the cause of accelerated trophoblast senescence remains unclear. The renin-angiotensin system (RAS) is closely related to organ senescence. Therefore, in the present study, we hypothesized that angiotensin (Ang)II, one of the most important RAS family members, accelerates trophoblast senescence through the transforming growth factor β-1 (TGF-β1) pathway.
Methods:
AngII and Ang1-7 were used to stimulate pregnant rats. AngII and its inhibitor olmesartan were used to stimulate trophoblast. Thereafter, senescence levels were measured. Furthermore, we used AngII to stimulate trophoblast and utilized RNA-sequencing (RNAseq) to analyze the expression of differentially expressed genes (DEGs). After identifying the overlapping genes by comparing the DEGs and senescence-related genes, we employed CytoHubba software to calculate the top five hub genes and selected TGF-β1 as the target gene. We transfected the AngII-stimulated trophoblast with TGF-β1 small interfering RNA (siRNA) and measured the senescence levels.
Results:
Senescence markers were upregulated in the AngII group compared with that in the control group. Furthermore, following AngII stimulation and RNAseq measurement, we identified 607 DEGs and 13 overlapping genes. The top five hub genes were as follows: PLAU, PTGS2, PDGF-β, TGF-β1, and FOXO3. Upon knockdown of TGF-β1 expression in AngII-stimulated trophoblast using TGF-β1 siRNA, we observed a downregulation of p53 and p62 mRNA expression.
Discussion:
AngII accelerates trophoblast senescence through the TGF-β1 pathway.
Insights
Angiotensin II (AngII) accelerates trophoblast senescence, a key factor in pregnancy outcomes, by activating the transforming growth factor β-1 (TGF-β1) pathway. This finding clarifies a mechanism behind pregnancy complications.
Area of Science:
- Reproductive biology
- Cellular senescence
- Molecular endocrinology
Background:
- Accelerated trophoblast senescence is linked to adverse pregnancy outcomes.
- The underlying mechanisms driving trophoblast senescence are not fully understood.
- The renin-angiotensin system (RAS) is implicated in organ senescence.
Purpose of the Study:
- To investigate the role of angiotensin II (AngII) in accelerating trophoblast senescence.
- To elucidate the involvement of the transforming growth factor β-1 (TGF-β1) pathway in AngII-induced trophoblast senescence.
Main Methods:
- Pregnant rats and isolated trophoblasts were stimulated with AngII.
- Senescence levels were assessed, and RNA sequencing (RNAseq) identified differentially expressed genes (DEGs).
- The role of TGF-β1 was confirmed by siRNA knockdown experiments.
Main Results:
- AngII stimulation led to increased senescence markers in trophoblasts.
- RNAseq identified 607 DEGs, with TGF-β1 identified as a key hub gene.
- Knockdown of TGF-β1 reduced AngII-induced upregulation of p53 and p62 mRNA.
Conclusions:
- Angiotensin II accelerates trophoblast senescence.
- The transforming growth factor β-1 pathway mediates AngII-induced trophoblast senescence.
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