Osteopontin Splicing Isoforms Contribute to Endometriotic Proliferation, Migration, and Epithelial-Mesenchymal Transition in Endometrial Epithelial Cells.
Nguyen-Tuong HoShu-Wei LinYi-Rong LeeChii-Ruey TzengShu-Huei KaoPublished in: International journal of molecular sciences (2022)
Osteopontin (OPN) isoforms, including OPNb and OPNc, promote malignancy and may contribute to the pathogenesis of endometriosis, a benign disorder with multiple characteristics resembling malignant tumors. In our experiments, OPNb and OPNc were significantly overexpressed in both endometriosis and adenomyosis compared to the normal endometrium. Upregulation of CD44v and the epithelial-mesenchymal transition (EMT) process was also present in endometriotic lesions. Overexpression of OPNb and OPNc splicing variants in endometriotic cells evoked morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding OPN ligand receptors CD44 and αvβ3, subsequently activating the PI3K and NF-ĸB pathways. We elucidated the causal role of OPN splice variants in regulating endometriotic cell growth, which may promote the development of OPN-targeted therapies for patients suffering from endometriotic disorders.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- induced apoptosis
- cell migration
- cell proliferation
- pi k akt
- transforming growth factor
- cell cycle arrest
- end stage renal disease
- copy number
- chronic kidney disease
- prognostic factors
- peritoneal dialysis
- cell cycle
- inflammatory response
- gene expression
- binding protein
- toll like receptor
- patient reported outcomes
- endoplasmic reticulum stress
- dna methylation
- nuclear factor
- genome wide