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Cellular Changes Consistent With Epithelial–Mesenchymal Transition and Fibroblast-to-Myofibroblast Transdifferentiation in the Progression of Experimental Endometriosis in Baboons
- Source :
- Reproductive Sciences. 23:1409-1421
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- We have recently shown that platelets play important roles in development of endometriosis and proposed that endometriotic lesions are essentially wounds that undergo repeated tissue injury and repair (ReTIAR). Further investigation indicated that endometriotic lesions, stimulated by platelet-derived transforming growth factor β1 (TGF-β1), activate the TGF-β1/Smad3 signaling pathway and undergo epithelial–mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT), resulting in increased cellular contractility and collagen production and increased smooth muscle metaplasia (SMM), leading to fibrosis. Using serially dissected endometriotic tissue samples from baboons with induced endometriosis, we tested the hypothesis of progressive EMT, FMT, SMM, and fibrosis through TGF-β1/Smad activation using immunohistochemistry and immunoflurescence staining analyses. We found that platelets are aggregated in endometriotic lesions, and vimentin expression was increased in the epithelial compartment of the lesions as they progressively developed. We also found that the number of smooth muscle cells (SMCs) appeared to increase with time as lesions progressed and was concomitant with the increased vimentin-positive glandular epithelial cells in the lesions. As lesion development progressed, TGF-β1 and phosphorylated-Smad3 staining was elevated and the number of α-smooth muscle actin-positive myofibroblasts and highly differentiated SMCs increased in the stromal compartment, which correlated with the increasing extent of fibrosis. These results, taken together, provide support for the notion that ReTIAR occurs in the endometriotic lesions, resulting in EMT and FMT, leading to SMM and ultimately fibrosis as lesions progress. Consequently, our data also provide corroborative evidence that platelets drive the EMT and FMT in endometriotic lesions over time, promoting SMM and resulting ultimately in fibrosis in the endometriotic lesions. These findings cast a new light on the natural history of endometriosis which so far has been elusive.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Stromal cell
Endometriosis
Vimentin
Transforming Growth Factor beta1
Lesion
03 medical and health sciences
0302 clinical medicine
Fibrosis
Metaplasia
medicine
Animals
Smad3 Protein
Epithelial–mesenchymal transition
Myofibroblasts
030219 obstetrics & reproductive medicine
biology
Transdifferentiation
Obstetrics and Gynecology
Epithelial Cells
Muscle, Smooth
Original Articles
Fibroblasts
medicine.disease
Disease Models, Animal
030104 developmental biology
Platelet Glycoprotein GPIb-IX Complex
Cell Transdifferentiation
Disease Progression
biology.protein
Female
medicine.symptom
Myofibroblast
Papio
Signal Transduction
Subjects
Details
- ISSN :
- 19337205 and 19337191
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Reproductive Sciences
- Accession number :
- edsair.doi.dedup.....ec1efdf3de5f99bfd5a1930d154cbaae