Journalartikel
Autorenliste: Mwaura, Agnes N.; Riaz, Muhammad A.; Maoga, Jane B.; Mecha, Ezekiel; Omwandho, Charles O. A.; Scheiner-Bobis, Georgios; Meinhold-Heerlein, Ivo; Konrad, Lutz
Jahr der Veröffentlichung: 2022
Zeitschrift: Biology
Bandnummer: 11
Heftnummer: 4
eISSN: 2079-7737
Open Access Status: Gold
DOI Link: https://doi.org/10.3390/biology11040513
Verlag: MDPI
Abstract:
Endometriosis is characterized by the presence of ectopic endometrium most often in the pelvis. The transforming growth factor-beta (TGF-beta) superfamily is also involved in the pathogenesis; however, betaglycan (BG, syn. TGF-beta type III receptor) as an important co-receptor was not studied. We analyzed mainly BG ectodomain shedding because released soluble BG (sBG) often antagonizes TGF-beta signaling. Furthermore, we studied the role of TGF-beta s and BG in wound healing and evaluated the suitability of BG measurements in serum and endocervical mucus for non-invasive diagnosis of endometriosis. Evaluation of the BG shedding and signaling pathways involved as well as wound healing was performed with enzyme-linked immune assays (ELISAs), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown, and scratch assays with human endometriotic epithelial cells. TGF-beta 1 /2 stimulation resulted in a significant dose-dependent reduction in BG shedding in endometriotic cells, which was TGF-beta/activin receptor-like kinase-5 (ALK-5)/mother against decapentaplegic homolog3 (SMAD3)- but not SMAD2-dependent. Inhibition of matrix metalloproteinases (MMPs) using the pan-MMP inhibitor GM6001 and tissue inhibitor of MMPs (TIMP3) equally attenuated BG shedding, signifying the involvement of MMPs in shedding. Likewise, recombinant BG moderately reduced the secretion of TGF-beta 1/2 and wound healing of endometriotic cells. TGF-beta 1 significantly enhanced the secretion of MMP2 and MMP3 and moderately promoted wound healing. In order to evaluate the role of BG in endometriosis, serum (n = 238) and mucus samples (n = 182) were analyzed. Intriguingly, a significant reduction in the levels of sBG in endocervical mucus but not in the serum of endometriosis patients compared to controls was observed. Collectively, these observations support a novel role for BG in the pathophysiology of endometriosis.
Zitierstile
Harvard-Zitierstil: Mwaura, A., Riaz, M., Maoga, J., Mecha, E., Omwandho, C., Scheiner-Bobis, G., et al. (2022) Role of Betaglycan in TGF-β Signaling and Wound Healing in Human Endometriotic Epithelial Cells and in Endometriosis, Biology, 11(4), Article 513. https://doi.org/10.3390/biology11040513
APA-Zitierstil: Mwaura, A., Riaz, M., Maoga, J., Mecha, E., Omwandho, C., Scheiner-Bobis, G., Meinhold-Heerlein, I., & Konrad, L. (2022). Role of Betaglycan in TGF-β Signaling and Wound Healing in Human Endometriotic Epithelial Cells and in Endometriosis. Biology. 11(4), Article 513. https://doi.org/10.3390/biology11040513
