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The Overexpression of TGF-β and CCN2 in Intrauterine Adhesions Involves the NF-κB Signaling Pathway.

Xue X, Chen Q, Zhao G, Zhao JY, Duan Z, Zheng PS - PLoS ONE (2015)

Bottom Line: Intrauterine adhesions (IUA) are a significant cause of menstrual disturbance and infertility, but their pathogenesis still remains unclear.Additionally, the expression of TGF-β and CCN2 was associated with IUA recurrence, which provides a potential prognostic indictor for IUA.Together, these results demonstrated that TGF-β and CCN2 play an important role in IUA formation, whose mechanism was associated with the activation of the NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology and Obstetrics, the Second Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, the People's Republic of China.

ABSTRACT
Intrauterine adhesions (IUA) are a significant cause of menstrual disturbance and infertility, but their pathogenesis still remains unclear. Here, we investigated the expression of TGF-β and CCN2 in IUA endometrial tissue by immunohistochemistry, western blotting and qRT-PCR assays, and found the expression of TGF-β and CCN2 in the endometrial tissue of IUA was significantly increased compared to normal endometrium and uterine septum (P<0.01), suggesting that TGF-β and CCN2 may play an important role in the formation of IUA. Moreover, the activity of the NF-κB signaling pathway in endometrial tissue of IUA was also significantly enhanced compared to normal endometrial and uterine septum (P<0.01) and positively correlated with the expression of TGF-β and CCN2, which suggested that TGF-β and CCN2 expression may be involved in the NF-κB signaling pathway. Blocking the NF-κB signaling pathway using SN50 resulted in the reduced expression of TGF-β in RL95-2 cells, which confirmed the association of the NF-κB signaling pathway and TGF-β in endometrial cells. Additionally, the expression of TGF-β and CCN2 was associated with IUA recurrence, which provides a potential prognostic indictor for IUA. Together, these results demonstrated that TGF-β and CCN2 play an important role in IUA formation, whose mechanism was associated with the activation of the NF-κB signaling pathway.

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The activity of the NF-κB signaling pathway was enhanced in IUA endometrial tissue.IκB-α, p-IκB-α and p65 protein expression in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by western blotting. Representative blots are shown (A, C), and either β-actin or lamin was used as a loading control. (B, D) The relative expression of IκB-α, p-IκB-α and p65 in endometrial tissue was calculated through normalization to β-actin or lamin. Results are expressed as the mean±SD. One way ANOVA(Tukey’ post hoc test); * P<0.05, ** P<0.01 vs. normal endometrium, # P<0.05, ## P<0.01 vs. uterine septum.
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pone.0146159.g003: The activity of the NF-κB signaling pathway was enhanced in IUA endometrial tissue.IκB-α, p-IκB-α and p65 protein expression in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by western blotting. Representative blots are shown (A, C), and either β-actin or lamin was used as a loading control. (B, D) The relative expression of IκB-α, p-IκB-α and p65 in endometrial tissue was calculated through normalization to β-actin or lamin. Results are expressed as the mean±SD. One way ANOVA(Tukey’ post hoc test); * P<0.05, ** P<0.01 vs. normal endometrium, # P<0.05, ## P<0.01 vs. uterine septum.

Mentions: It has been reported that the NF-κB signaling pathway contributes to fibrogenesis[22]. However, the role of the NF-κB signaling pathway in IUA pathogenesis remains unclear. To clarify whether the NF-κB signaling pathway is involved in the formation of IUA, NF-κB signaling pathway activity in endometrial tissue was evaluated through the measurement of IκB-α, phosphorylated IκB-α(p-IκB-α) and p65 using western blotting. Representative blots are shown in Fig 3A and 3C. The relative expression of these proteins was calculated through normalization to β-actin or lamin, and are summarized in Fig 3B and 3D. The expression of IκB-α in the cytoplasm of IUA endometrial cells was significantly decreased compared to that seen in the normal endometrial tissue (P<0.01). In contrast, the expression of phosphorylated IκB-α(p-IκB-α) in the cytoplasm of IUA endometrial cells was significantly increased compared to normal endometrial tissue (P<0.01). Furthermore, the expression of p65 in the nuclei of IUA endometrial cells was markedly increased compared to that of the normal endometrial tissue (P<0.01). These data suggest that NF-κB signaling pathway activity in IUA endometrium was enhanced compared to normal endometrium.


The Overexpression of TGF-β and CCN2 in Intrauterine Adhesions Involves the NF-κB Signaling Pathway.

Xue X, Chen Q, Zhao G, Zhao JY, Duan Z, Zheng PS - PLoS ONE (2015)

The activity of the NF-κB signaling pathway was enhanced in IUA endometrial tissue.IκB-α, p-IκB-α and p65 protein expression in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by western blotting. Representative blots are shown (A, C), and either β-actin or lamin was used as a loading control. (B, D) The relative expression of IκB-α, p-IκB-α and p65 in endometrial tissue was calculated through normalization to β-actin or lamin. Results are expressed as the mean±SD. One way ANOVA(Tukey’ post hoc test); * P<0.05, ** P<0.01 vs. normal endometrium, # P<0.05, ## P<0.01 vs. uterine septum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697802&req=5

pone.0146159.g003: The activity of the NF-κB signaling pathway was enhanced in IUA endometrial tissue.IκB-α, p-IκB-α and p65 protein expression in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by western blotting. Representative blots are shown (A, C), and either β-actin or lamin was used as a loading control. (B, D) The relative expression of IκB-α, p-IκB-α and p65 in endometrial tissue was calculated through normalization to β-actin or lamin. Results are expressed as the mean±SD. One way ANOVA(Tukey’ post hoc test); * P<0.05, ** P<0.01 vs. normal endometrium, # P<0.05, ## P<0.01 vs. uterine septum.
Mentions: It has been reported that the NF-κB signaling pathway contributes to fibrogenesis[22]. However, the role of the NF-κB signaling pathway in IUA pathogenesis remains unclear. To clarify whether the NF-κB signaling pathway is involved in the formation of IUA, NF-κB signaling pathway activity in endometrial tissue was evaluated through the measurement of IκB-α, phosphorylated IκB-α(p-IκB-α) and p65 using western blotting. Representative blots are shown in Fig 3A and 3C. The relative expression of these proteins was calculated through normalization to β-actin or lamin, and are summarized in Fig 3B and 3D. The expression of IκB-α in the cytoplasm of IUA endometrial cells was significantly decreased compared to that seen in the normal endometrial tissue (P<0.01). In contrast, the expression of phosphorylated IκB-α(p-IκB-α) in the cytoplasm of IUA endometrial cells was significantly increased compared to normal endometrial tissue (P<0.01). Furthermore, the expression of p65 in the nuclei of IUA endometrial cells was markedly increased compared to that of the normal endometrial tissue (P<0.01). These data suggest that NF-κB signaling pathway activity in IUA endometrium was enhanced compared to normal endometrium.

Bottom Line: Intrauterine adhesions (IUA) are a significant cause of menstrual disturbance and infertility, but their pathogenesis still remains unclear.Additionally, the expression of TGF-β and CCN2 was associated with IUA recurrence, which provides a potential prognostic indictor for IUA.Together, these results demonstrated that TGF-β and CCN2 play an important role in IUA formation, whose mechanism was associated with the activation of the NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology and Obstetrics, the Second Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, the People's Republic of China.

ABSTRACT
Intrauterine adhesions (IUA) are a significant cause of menstrual disturbance and infertility, but their pathogenesis still remains unclear. Here, we investigated the expression of TGF-β and CCN2 in IUA endometrial tissue by immunohistochemistry, western blotting and qRT-PCR assays, and found the expression of TGF-β and CCN2 in the endometrial tissue of IUA was significantly increased compared to normal endometrium and uterine septum (P<0.01), suggesting that TGF-β and CCN2 may play an important role in the formation of IUA. Moreover, the activity of the NF-κB signaling pathway in endometrial tissue of IUA was also significantly enhanced compared to normal endometrial and uterine septum (P<0.01) and positively correlated with the expression of TGF-β and CCN2, which suggested that TGF-β and CCN2 expression may be involved in the NF-κB signaling pathway. Blocking the NF-κB signaling pathway using SN50 resulted in the reduced expression of TGF-β in RL95-2 cells, which confirmed the association of the NF-κB signaling pathway and TGF-β in endometrial cells. Additionally, the expression of TGF-β and CCN2 was associated with IUA recurrence, which provides a potential prognostic indictor for IUA. Together, these results demonstrated that TGF-β and CCN2 play an important role in IUA formation, whose mechanism was associated with the activation of the NF-κB signaling pathway.

Show MeSH
Related in: MedlinePlus