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Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus.

Feng H, Su R, Song Y, Wang C, Lin L, Ma J, Yang H - PLoS ONE (2016)

Bottom Line: The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT.We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia.The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

ABSTRACT
Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

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Immunohistochemistry of pIRS-1(Ser312) and pAKt in chorionic villi in maternal surface of normal control (n = 36) and GDM (n = 33).Protein of pIRS-1(Ser312) were expressed in trophoblast and endothelial cells of (A) the normal, and its expression increased in (B) GDM placentae. Phosphorylation of Akt protein was strongly expressed in (C) normal placentae, whereas it was absent or very faintly expressed in (D) GDM placentae. (E) The expression of CK7 in chorionic villi in maternal surface of placentae. (F) Negative control. The decrease mainly happened in trophoblasts (CK7+cells) but not endothelial cells of vessel. Sections were counterstained with hematoxylin (blue). All photomicrographs were taken at 400×magnification. STB, syncytiotrophoblast; BV: blood vascul.
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pone.0157185.g004: Immunohistochemistry of pIRS-1(Ser312) and pAKt in chorionic villi in maternal surface of normal control (n = 36) and GDM (n = 33).Protein of pIRS-1(Ser312) were expressed in trophoblast and endothelial cells of (A) the normal, and its expression increased in (B) GDM placentae. Phosphorylation of Akt protein was strongly expressed in (C) normal placentae, whereas it was absent or very faintly expressed in (D) GDM placentae. (E) The expression of CK7 in chorionic villi in maternal surface of placentae. (F) Negative control. The decrease mainly happened in trophoblasts (CK7+cells) but not endothelial cells of vessel. Sections were counterstained with hematoxylin (blue). All photomicrographs were taken at 400×magnification. STB, syncytiotrophoblast; BV: blood vascul.

Mentions: To investigate whether local insulin resistance of placentae alters for GDM patients, we examined the key molecules in the insulin pathway. Compared to the control (Fig 4A), pIRS-1(Ser312) staining in the placentae of GDM patients (Fig 4B) was significantly increased (mean OD: 0.034±0.005 vs 0.083±0.009, p<0.05), while the phosphorylation of Akt was significantly decreased (as control in Fig 4C & GDM in 4D) (mean OD: 0.022±0.007 vs 0.009±0.002, p<0.05). Moreover, these changes mainly happened in trophoblasts of chorionic villi (CK7+), as the increase of pIRS-1(Ser312) was shown in trophoblast; meanwhile, the signal of pAkt was obviously absent or minimal in trophoblasts of the GDM placentae, while showed no significant difference in vessel endothelial cells.


Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus.

Feng H, Su R, Song Y, Wang C, Lin L, Ma J, Yang H - PLoS ONE (2016)

Immunohistochemistry of pIRS-1(Ser312) and pAKt in chorionic villi in maternal surface of normal control (n = 36) and GDM (n = 33).Protein of pIRS-1(Ser312) were expressed in trophoblast and endothelial cells of (A) the normal, and its expression increased in (B) GDM placentae. Phosphorylation of Akt protein was strongly expressed in (C) normal placentae, whereas it was absent or very faintly expressed in (D) GDM placentae. (E) The expression of CK7 in chorionic villi in maternal surface of placentae. (F) Negative control. The decrease mainly happened in trophoblasts (CK7+cells) but not endothelial cells of vessel. Sections were counterstained with hematoxylin (blue). All photomicrographs were taken at 400×magnification. STB, syncytiotrophoblast; BV: blood vascul.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4920413&req=5

pone.0157185.g004: Immunohistochemistry of pIRS-1(Ser312) and pAKt in chorionic villi in maternal surface of normal control (n = 36) and GDM (n = 33).Protein of pIRS-1(Ser312) were expressed in trophoblast and endothelial cells of (A) the normal, and its expression increased in (B) GDM placentae. Phosphorylation of Akt protein was strongly expressed in (C) normal placentae, whereas it was absent or very faintly expressed in (D) GDM placentae. (E) The expression of CK7 in chorionic villi in maternal surface of placentae. (F) Negative control. The decrease mainly happened in trophoblasts (CK7+cells) but not endothelial cells of vessel. Sections were counterstained with hematoxylin (blue). All photomicrographs were taken at 400×magnification. STB, syncytiotrophoblast; BV: blood vascul.
Mentions: To investigate whether local insulin resistance of placentae alters for GDM patients, we examined the key molecules in the insulin pathway. Compared to the control (Fig 4A), pIRS-1(Ser312) staining in the placentae of GDM patients (Fig 4B) was significantly increased (mean OD: 0.034±0.005 vs 0.083±0.009, p<0.05), while the phosphorylation of Akt was significantly decreased (as control in Fig 4C & GDM in 4D) (mean OD: 0.022±0.007 vs 0.009±0.002, p<0.05). Moreover, these changes mainly happened in trophoblasts of chorionic villi (CK7+), as the increase of pIRS-1(Ser312) was shown in trophoblast; meanwhile, the signal of pAkt was obviously absent or minimal in trophoblasts of the GDM placentae, while showed no significant difference in vessel endothelial cells.

Bottom Line: The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT.We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia.The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

ABSTRACT
Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

No MeSH data available.


Related in: MedlinePlus