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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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TGF-β and CCN2 were overexpressed in IUA endometrial tissue.(A) The expression of TGF-β and CCN2 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. (B) A quantitative analysis of TGF-β and CCN2 expression in normal endometrium, uterine septum and intrauterine adhesions normalized to β-actin expression. The levels of TGF-β (C) and CCN2 (D) transcripts in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by qRT-PCR. 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.g002: TGF-β and CCN2 were overexpressed in IUA endometrial tissue.(A) The expression of TGF-β and CCN2 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. (B) A quantitative analysis of TGF-β and CCN2 expression in normal endometrium, uterine septum and intrauterine adhesions normalized to β-actin expression. The levels of TGF-β (C) and CCN2 (D) transcripts in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by qRT-PCR. 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: To further confirm the expression of TGF-β and CCN2 in endometrium, a western blot assay was performed, with a representative blot shown in Fig 2A. The relative expression of both TGF-β and CCN2 proteins was calculated through normalization to β-actin, as summarized in Fig 2B. Similar to the results of immunohistochemical staining, TGF-β and CCN2 proteins were strongly expressed in IUA endometrium (Mild, Moderate and Severe groups) and weakly expressed in normal endometrium and uterine septum. A quantitative analysis of TGF-β and CCN2 expression revealed that TGF-β and CCN2 protein expression levels in IUA endometrial tissues were significantly increased compared to those in normal endometrial tissues and uterine septum (P<0.01).


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)

TGF-β and CCN2 were overexpressed in IUA endometrial tissue.(A) The expression of TGF-β and CCN2 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. (B) A quantitative analysis of TGF-β and CCN2 expression in normal endometrium, uterine septum and intrauterine adhesions normalized to β-actin expression. The levels of TGF-β (C) and CCN2 (D) transcripts in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by qRT-PCR. 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

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

pone.0146159.g002: TGF-β and CCN2 were overexpressed in IUA endometrial tissue.(A) The expression of TGF-β and CCN2 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. (B) A quantitative analysis of TGF-β and CCN2 expression in normal endometrium, uterine septum and intrauterine adhesions normalized to β-actin expression. The levels of TGF-β (C) and CCN2 (D) transcripts in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by qRT-PCR. 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: To further confirm the expression of TGF-β and CCN2 in endometrium, a western blot assay was performed, with a representative blot shown in Fig 2A. The relative expression of both TGF-β and CCN2 proteins was calculated through normalization to β-actin, as summarized in Fig 2B. Similar to the results of immunohistochemical staining, TGF-β and CCN2 proteins were strongly expressed in IUA endometrium (Mild, Moderate and Severe groups) and weakly expressed in normal endometrium and uterine septum. A quantitative analysis of TGF-β and CCN2 expression revealed that TGF-β and CCN2 protein expression levels in IUA endometrial tissues were significantly increased compared to those in normal endometrial tissues and uterine septum (P<0.01).

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