TGF-β1 Increases Cell Adhesion and Drives Disease ProgressionBy: Kasthuri Nair - Sep 27, 2017
TGF-β1 controls the signaling cascade that results in the increased adhesion of endometrial cells to mesothelium in endometriosis.
- This study seeks to understand the role of TGF-β1 in endometrial cell adhesion to the mesothelium.
- The molecular mechanisms that drive endometriosis disease progression are still at large. Elucidating this mechanism or part of it will allow researchers to create more targeted therapies.
What’s done here?
- The researchers cultured three different cell lines: Immortalized normal human endometrial cells (HES cells), immortalized human endometriotic epithelial cells (12Z), and human mesothelial Met5A cells.
- Total RNA was taken from the HES cells and 12Z cells. The RNA was then subject to reverse transcription-polymerase chain reaction (RT-PCR).
- The researchers removed all the total protein from the cells, and the protein was then subject to Western Blot analysis.
- Other parts of the experiment consisted of cell adhesion assays and antibody neutralization.
- The quantitative data from this experiment examined by the statistical analysis.
- Endometriotic cells had higher TGF-β1 expression and higher cell adhesion efficiency.
- The results showed that activation of the TGF- β1/TGF- βRI/Smad2 signaling pathway controls the following integrins: αV, α6, β1, and β4. It is important to note that this signaling cascade is controlled by TGF-β1 and results in increased cell adhesion. Neutralizing antibodies against the integrins αV, β1, and β4 can counteract the process mentioned above.
- Indubitably, this study shows that TGF-β1 plays a role in endometriosis disease progression via integrin controlled cell adhesion.
Limitations of the study:
- This experiment was conducted in vitro and thus cannot entirely mimic the environment in which this process would occur.
Without a doubt, the mechanism that drives endometriosis disease progression is complicated. Choi et al. look to elucidate one part of this complex process. They seek to understand the role of transforming growth factor β1 (TGF-β1) in the initial adhesion of endometrial cells to the mesothelium. The authors published their findings in an article titled “Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression” in the BMB Reports.
The experiment started with cell culture. The cells were then subject to reverse transcriptase-polymerase chain reaction. After that, the protein was isolated from the cells and western blot analysis was conducted. The researchers also used cell adhesion assays and antibody neutralization. All quantitative data were subject to statistical analysis.
The results show that TGF-β1 was expressed more in the endometriotic cells. Furthermore, endometriotic cells had higher adhesion efficiency. The researchers also found that activation of the TGF- β1/TGF- βRI/Smad2 signaling pathway led to the managed the activity of integrins αV, α6, β1, and β4. This activation mentioned above is controlled by TGF-β1 and results in the adhesion of endometrial cells. On the other hand, neutralizing antibodies against the integrins αV, β1, and β4 counteracted the adhesion process.
"We, therefore, propose that TGF-β1-stimulation of integrins αV, α6, β1, and β4 could be a good target for the development of new methods aimed at preventing or treating endometriosis", authors concluded.
Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28760197
TGF-?1 cell adhesion integrin