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

CTRP6, a member of the C1q/TNF-related protein (CTRP) family, has gained increasing scientific interest because of its regulatory role in tumor progression. Previous studies have shown that CTRP6 is closely involved in regulating various pathophysiological processes, including glucose and lipid metabolism, cell proliferation, apoptosis, and inflammation. To date, CTRP6 has been identified as related to eight different malignancies, including lung cancer, oral cancer, gastric cancer, colon cancer, liver cancer, bladder cancer, renal cancer, and ovarian cancer. CTRP6 is reported to be associated with tumor progression by activating a series of related signal networks. This review article mainly discusses the biochemistry and pleiotropic pathophysiological functions of CTRP6 as a new molecular mediator in carcinogenesis, hoping that the information summarized herein could make a modest contribution to the development of novel cancer treatments in the future.

C1q/TNF-related protein 6 (CTRP6) attenuates renal ischaemia-reperfusion injury through the activation of PI3K/Akt signalling pathway.

C1q/TNF-related protein 6 (CTRP6) is a member of the CTRP family that has been reported to exhibit a nephroprotective effect. However, the role of CTRP6 in renal ischaemia/reperfusion (I/R) injury (IRI) remains unclear. In the present study, we aimed to explore the protective effect of CTRP6 in renal IRI and the potential mechanism. We found that CTRP6 expression was markedly decreased in the kidneys of mice subjected to I/R and HK-2 cells in response to hypoxia/reoxygenation (H/R) stimulation. Recombinant CTRP6 protein protected against renal I/R injury by the reduction of blood urea nitrogen (BUN) and creatinine levels. The increased production of ROS and malondialdehyde (MDA), as well the decreased activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) caused by H/R induction were mitigated by CTRP6 in HK-2 cells. The caspase-3 activity and apoptotic rate were both decreased in CTRP6-overexpressing HK-2 cells. In addition, we also found that knockdown of CTRP6 aggravated H/R-caused oxidative stress and cell apoptosis in HK-2 cells. Moreover, CTRP6 overexpression enhanced the H/R-stimulated activation of PI3K/Akt pathway in HK-2 cells. Inhibition of PI3K reversed the nephroprotective effects of CTRP6 in HK-2 cells. Taken together, CTRP6 exerted protective effects against H/R-caused oxidative injury in HK-2 cells via activating the PI3K/Akt pathway.

Relationship between serum CTRP6 level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective@#To explore the relationship between serum C1q and tumor necrosis factor related protein 6(CTRP6) level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus (T2DM).@*Methods@#A total of 167 patients with newly diagnosed T2DM in the outpatient department of our hospital were recruited from April 2016 to March 2017 and 165 subjects with normal glucose tolerance were used as the control group. The concentrations of CTRP6, interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) were determined by ELISA.@*Results@#Circulating CTRP6 level was significantly higher in T2DM group than that in control group [(652.54±132.57) vs (521.28±119.93)μg/L, P<0.01] after adjusting age and body mass index (BMI). Overweight/obese subjects revealed higher CTRP6 levels compared with those in lean individuals. In addition, circulating CTRP6 level was positively correlated with BMI, waist circumference, fasting plasma glucose, postprandial 2h plasma glucose, HbA1C, fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride (TG), IL-6, MCP-1, highly sensitive C-reactive protein (hs-CRP), and TNF-α, while it was inversely correlated with high-density lipoprotein-cholesterol(P<0.01). Multivariate linear regression analysis showed that TG, HOMA-IR, and IL-6 were independent factors for CTRP6 level. After adjusting for potential confounders, CTRP6 remained an independent risk factor for T2DM. Trend test showed that the increase in CTRP6 level was significantly linear with the occurrence of T2DM. The analysis of receiver operating characteristic curves revealed that the area under the curve for circulating CTRP6 to predict T2DM was 0.730.@*Conclusions@#CTRP6 may be associated with insulin resistance.

Relationship between serum CTRP6 level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective To explore the relationship between serum C1q and tumor necrosis factor related protein 6 ( CTRP6 ) level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods A total of 167 patients with newly diagnosed T2DM in the outpatient department of our hospital were recruited from April 2016 to March 2017 and 165 subjects with normal glucose tolerance were used as the control group. The concentrations of CTRP6, interleukin 6 (IL-6), monocyte chemoattractant protein-1 ( MCP-1), and tumor necrosis factor a( TNF-α) were determined by ELISA. Results Circulating CTRP6 level was significantly higher in T2DM group than that in control group [(652.54 ± 132.57) vs ( 521.28 ± 119.93) μg/L, P＜0.01] after adjusting age and body mass index (BMI). Overweight/obese subjects revealed much higher CTRP6 levels compared with those in lean individuals. In addition, circulating CTRP6 level was positively correlated with BMI, waist circumference, fasting plasma glucose, postprandial 2h plasma glucose, HbA1C, fasting insulin, homeostasis model assessment insulin resistance index ( HOMA-IR), triglyceride ( TG), IL-6, MCP-1, highly sensitive C-reactive protein ( hs-CRP ), and TNF-α, while it was inversely correlated with high-density lipoprotein-cholesterol ( P＜0.01). Multiple linear regression analysis showed that TG, HOMA-IR, and IL-6 were independent factors for CTRP6 level. After adjusting for potential confounders, CTRP6 remains an independent risk factor for T2DM. Trend detection showed that the increase in CTRP6 level was significantly linear with the occurrence of T2DM. The analysis of receiver operating characteristic curves revealed that the area under the curve for circulating CTRP6 to predict T2DM was 0.730. Conclusions CTRP6 may be associated with insulin resistance.

Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats.

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction.