Tissue Transglutaminase (TG2) as a Candidate Biomarker and Potential Therapeutic Target in Endometriosis: Functional Evidence from shRNA-Mediated Downregulation of TG2 in Endometrial Mesenchymal Stem Cells.
- 1Department of Genetics and Bioengineering, Yeditepe University, 26 August Campus, Kayisdagi, Atasehir, Istanbul 34755, Türkiye.
- 2Department of Biotechnology, Faculty of Pharmacy, Istanbul Okan University, Tuzla, Istanbul 34959, Türkiye.
Abstract
Background/Objectives: Endometriosis involves the presence of endometrial tissue outside the uterus. Since the migration of endometrial cells is pivotal to lesion development, tissue transglutaminase (TG2)-known for its roles in cell adhesion, migration, and stemness-may play a significant role. This study aimed to investigate the involvement of TG2 in the migratory and invasive characteristics of endometrial mesenchymal stem cells (eMSCs) derived from healthy individuals and endometriosis patients. Methods: eMSCs were isolated from healthy controls (heMSCs) and endometriosis patients (peMSCs). TG2 protein expression and enzyme activity were evaluated. Co-immunoprecipitation (Co-IP) experiments were performed to assess TG2 associations with ITGβ-1 and SDC-4 in membrane fractions. Additionally, shRNA technology was utilized to silence TG2 in peMSCs to analyze its effects on cell proliferation, migration, invasion, and matrix metalloproteinase (MMP-2 and -9) activities. Results: peMSCs exhibited higher TG2 protein expression but lower enzyme activity compared to heMSCs. Co-IP analysis of membrane fractions revealed enhanced association of TG2 with ITGβ-1 and SDC-4 in peMSCs, thereby promoting enhanced cell survival, migration, and invasive properties. Silencing TG2 in peMSCs via shRNA eliminated these enhanced proliferation, migration, and invasion capabilities, reverting them to a phenotype resembling heMSCs. Furthermore, elevated MMP-2 and -9 activities returned to basal levels following TG2 knockdown. Conclusions: These findings suggest that TG2 acts as a distinctive cell adhesion molecule directly involved in endometriosis pathogenesis. Collectively, these findings identify TG2 as a disease-associated molecular marker warranting further evaluation for its diagnostic potential and suggest that targeting its cell-adhesion functions may represent a novel therapeutic strategy for endometriosis.
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BibTeX
@article{kurtcelep2026tissue,
title = {{Tissue Transglutaminase (TG2) as a Candidate Biomarker and Potential Therapeutic Target in Endometriosis: Functional Evidence from shRNA-Mediated Downregulation of TG2 in Endometrial Mesenchymal Stem Cells.}},
author = {İnci Kurt-Celep and Melike Batukan and Fikrettin Şahin and Dilek Telci},
journal = {Pharmaceuticals (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/ph19101520},
url = {https://europepmc.org/article/MED/42943217},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tissue Transglutaminase (TG2) as a Candidate Biomarker and Potential Therapeutic Target in Endometriosis: Functional Evidence from shRNA-Mediated Downregulation of TG2 in Endometrial Mesenchymal Stem Cells.
AU - İnci Kurt-Celep
AU - Melike Batukan
AU - Fikrettin Şahin
AU - Dilek Telci
PY - 2026
DA - 2026/09/25
JO - Pharmaceuticals (Basel, Switzerland)
DO - 10.3390/ph19101520
UR - https://europepmc.org/article/MED/42943217
AB - Background/Objectives: Endometriosis involves the presence of endometrial tissue outside the uterus. Since the migration of endometrial cells is pivotal to lesion development, tissue transglutaminase (TG2)-known for its roles in cell adhesion, migration, and stemness-may play a significant role. This study aimed to investigate the involvement of TG2 in the migratory and invasive characteristics of endometrial mesenchymal stem cells (eMSCs) derived from healthy individuals and endometriosis patients. Methods: eMSCs were isolated from healthy controls (heMSCs) and endometriosis patients (peMSCs). TG2 protein expression and enzyme activity were evaluated. Co-immunoprecipitation (Co-IP) experiments were performed to assess TG2 associations with ITGβ-1 and SDC-4 in membrane fractions. Additionally, shRNA technology was utilized to silence TG2 in peMSCs to analyze its effects on cell proliferation, migration, invasion, and matrix metalloproteinase (MMP-2 and -9) activities. Results: peMSCs exhibited higher TG2 protein expression but lower enzyme activity compared to heMSCs. Co-IP analysis of membrane fractions revealed enhanced association of TG2 with ITGβ-1 and SDC-4 in peMSCs, thereby promoting enhanced cell survival, migration, and invasive properties. Silencing TG2 in peMSCs via shRNA eliminated these enhanced proliferation, migration, and invasion capabilities, reverting them to a phenotype resembling heMSCs. Furthermore, elevated MMP-2 and -9 activities returned to basal levels following TG2 knockdown. Conclusions: These findings suggest that TG2 acts as a distinctive cell adhesion molecule directly involved in endometriosis pathogenesis. Collectively, these findings identify TG2 as a disease-associated molecular marker warranting further evaluation for its diagnostic potential and suggest that targeting its cell-adhesion functions may represent a novel therapeutic strategy for endometriosis.
SN - 1424-8247
ER -