C1q/tumor necrosis factor related protein 6 (CTRP6) regulates the phenotypes of high glucose-induced gestational trophoblast cells via peroxisome proliferator-activated receptor gamma (PPARγ) signaling

Abstract

Multiple studies have confirmed that adipokines are compactly relevant to insulin resistance and participate in the pathogenesis of gestational diabetes mellitus (GDM). This paper aimed to study the effects of C1q/tumor necrosis factor related protein (CTRP)6 on the phenotypes of trophoblast cells, covering cell proliferation, invasion and migration, and initially explore the mechanism. High glucose was used to induce trophoblast cells to establish an in vitro model. The expression levels of CTRP6 were firstly determined, and then the effects of CTRP6 knockdown on cell viability, apoptosis, migration and invasion were assessed using CCK8, TUNEL, wound healing, Transwell assays. Moreover, the role of peroxisome proliferator-activated receptor gamma (PPARγ), probable target of CTRP6, was evaluated through co-transfection with PPARγ overexpression vector. The results of the present study revealed that CTRP6 and PPARγ were both upregulated in high glucose-induced cells. And CTRP6 knockdown could significantly elevate the abilities of cell viability, migration and invasion, and avoid cell apoptosis. In addition, PPARγ overexpression was found to restrain the protective effects of CTRP6 knockdown on the above aspects, indicating CTRP6 played a role in trophoblast cells via inhibiting PPARγ expression. In conclusion, CTRP6 regulated the viability, migration and invasion of high glucose-induced gestational trophoblast cells through PPARγ signaling.

Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus

“…Emerging evidence suggests that CTRP6 is also highly expressed in placenta [13,17,22]. Furthermore, Zhang Jin et al reported that CTRP6 was up-regulated in high glucoseinduced trophoblast cells [22]. Consistent with this, our study showed that with the increase in placental weight in GDM patients, the expression of CTRP6 was up-regulated.…”

“…Emerging evidence suggests that CTRP6 is also highly expressed in placenta [13,17,22]. Furthermore, Zhang Jin et al reported that CTRP6 was up-regulated in high glucoseinduced trophoblast cells [22].…”

“…However, compared with the studies on obesity and T2DM, there are relatively few studies on the role of CTRP6 in GDM, although obesity has been generally considered to be inseparable from GDM. Recently, CTRP6 was found to regulate the viability, migration and invasion of high glucose-induced gestational trophoblast cells via inhibiting PPARγ expression, indicating that CTRP6 may play an important role in GDM [22]. Our previous study demonstrated that CTRP6 expression in the adipose tissue of pregnant rats is significantly correlated with blood glucose levels [23].…”

Effect of 23‑hydroxybetulinic acid on lung adenocarcinoma and its mechanism of action

“…The results indicated that PPAR-γ silencing promoted Colo16 cell proliferation and reduced apoptosis, whereas PPAR-γ overexpression exhibited the opposite effects. Therefore, PPAR-γ serves a role in inhibiting tumor cell proliferation and promoting apoptosis in human squamous cell carcinoma Colo16 cells ( 50 ). The conclusions of the present study align with these findings.…”

Advances in the functions of CTRP6 in the development and progression of the malignancy

“…In female tissues, CTRP6 protein is most highly expressed in the placenta endothelial cells and syncytiotrophoblasts. CTRP6 regulated the viability, migration, and invasion of human chorion trophoblast cells through PPARγ signaling ( Zhang and Bai, 2022 ). In the endometrium, stroma cells but not glandular cells show high expression of CTRP6.…”