C1q Tumor Necrosis Factor-related Protein Research Articles

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.

Updates in diabetic neuropathy: A call for new diagnostic and treatment approaches.

Diabetic polyneuropathy (DPN) is a serious complication of both type 1 and type 2 diabetes. The major clinical manifestations of DPN are neuropathic pain, diabetic foot (which is associated with ulcers, gangrene, and amputation), and autonomic neuropathy. Diabetic sensorimotor peripheral neuropathy (DSPN) is the most common form of DPN and affects approximately 50% of people with type 1 or 2 diabetes during their lifetime (1) . Despite its major clinical impact, DPN remains underdiagnosed and undertreated. To reduce the burdens of DPN, there is an urgent need to develop both novel diagnostic procedures that enable to improve the early detection of the disease and new treatments that address multiple mechanistic pathways (Figure) (2) .

C1q Tumor Necrosis Factor-Related Protein 1: A Promising Therapeutic Target for Atherosclerosis.

Atherosclerosis serves as the pathological basis of most cardiovascular and cerebrovascular diseases. C1q tumor necrosis factor-related protein 1 (CTRP1) is a 35-kDa glycoprotein synthesized by various tissues and cells, such as adipose tissue and macrophages. As an adiponectin paralog, CTRP1 signals through adiponectin receptor 1 and participates in a variety of pathophysiological processes. Circulating CTRP1 levels are significantly increased in patients with coronary artery disease. Importantly, CTRP1 was shown to accelerate the development of atherosclerosis by promoting vascular inflammation, macrophage foam cell formation, and endothelial barrier dysfunction. This review focused on recent advances regarding the role of CTRP1 in atherogenesis with an emphasis on its potential as a novel biomarker and a promising therapeutic target for atherosclerosis-related diseases.

Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke.

Introduction C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. MethodsA total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis.ResultsWe found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes.ConclusionsAll the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS.Trial RegistrationChinese Clinical Trial Registry, ChiCTR1800020330.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00296-7.

Features of Changes in the Structural and Functional State of the Myocardium in Patients with Acute Myocardial Infarction Depending on Body Mass Index Considering FABP4 and CTRP3 Levels

Introduction. Adipokines such as fatty acid-binding protein 4 (FABP4) and C1q tumor necrosis factor-related protein 3 (CTRP3) can affect the structural and functional state of the myocardium in patients with acute myocardial infarction and obesity.
 The objective of the research was to determine the relationship between FABP4, CTRP3 and echocardiographic parameters of the left ventricular myocardium in patients with acute myocardial infarction depending on body mass index.
 Materials and Methods. The observational cross-sectional study examined 189 patients with acute myocardial infarction depending on body mass index, who were divided into the following groups: Group 1 included 60 patients with acute myocardial infarction and normal body mass index; Group 2 comprised 68 patients with acute myocardial infarction and excess body weight; Group 3 included 61 patients with acute myocardial infarction and obesity.
 Results. In Group 1, the statistical significance correlations were found: between FABP4 and end-diastolic dimension (EDD; r = -0.458), end-systolic dimension (ESD; r = -0.460), end-diastolic volume (EDV; r = -0.452), left ventricular myocardial mass (LVMM; r = -0.411), LVMM/body surface area index (LVMMI2; r = -0.419); between CTRP3 and EDV (r = 0.425), EDD (r = 0.469), left ventricular relative posterior wall thickness (LVRPWT; r = -0.469). In Group 2, there were found the statistical significance relationships between: FABP4 and EDD (r = 0.461), ESD (r = 0.467), EDV (r = 0.449), end-systolic volume (ESV; r = 0.485), LVMM (r = 0.487), LVMMI1 (r = 0.406); between CTRP3 and EDD (r = -0.440), EDV (r = -0.413), LVMM (r = -0.430), LVMM/height2.7 index (LVMMI1; r = -0.483). In Group 3, the statistical significance correlations were found between: FABP4 and EDV (r = 0.481), ESD (r = 0.411), ESV (r = 0.490), LVMMI1 (r = 0.403); between CTRP3 and EDV (r = -0.326), ESD (r = -0.367), ESV (r = -0.453), LVMMI1 (r = -0.415).
 Conclusions. In patients with acute myocardial infarction and overweight/obesity, echocardiographic parameters had a significant low positive correlation with FABP4 and a low negative correlation with CTRP3. On the contrary, in patients with acute myocardial infarction and normal body mass index, echocardiographic parameters had a significant low negative correlation with FABP4 and a low positive correlation with CTRP3.

C1q/tumor necrosis factor-related protein-3 improves microvascular endothelial function in diabetes through the AMPK/eNOS/NO· signaling pathway

The repair of vascular endothelial cell dysfunction is an encouraging approach for the treatment of vascular complications associated with diabetes. It has been demonstrated that members of C1q/tumor necrosis factor-related protein (CTRP) family may improve endothelial function. Nevertheless, the protective properties of CTRPs in diabetic microvascular complications continue to be mostly unknown. Here, we demonstrate that the C1q-like globular domain of CTRP3, CTRP5, and CTRP9 (gCTRP3, 5, 9) exerted a vasorelaxant effect on the microvasculature, of which gCTRP3 was the most powerful one. In a murine model of type 2 diabetes mellitus, serum gCTRP3 level and endothelial function decreased markedly compared with controls. Two weeks of gCTRP3 treatment (0.5 μg/g/d) enhanced endothelium-dependent relaxation in microvessels, increased nitric oxide (NO·) production, and reduced retinal vascular leakage. In addition, Western blotting in human retinal microvascular endothelial cells indicated that gCTRP3 triggered AMP-activated protein kinase-α (AMPKα), hence increasing the endothelial NO synthase (eNOS) level and NO· production. In addition, incubation with gCTRP3 in vitro ameliorated the endothelial dysfunction induced by high glucose in the branch of the mesenteric artery. Blockade of either eNOS or AMPKα completely abolished the effects of gCTRP3 described above. Taken together, we demonstrate for the first time that gCTRP3 improves impaired vasodilatation of microvasculature in diabetes by ameliorating endothelial cell function through the AMPK/eNOS/NO· signaling pathway. This finding may suggest an effective intervention against diabetes-associated microvascular complications.

Role of the CTRP family in tumor development and progression.

C1q tumor necrosis factor-related proteins (CTRPs), which are members of the adipokine superfamily, have gained significant interest in the recent years. CTRPs are homologs of adiponectin with numerous functions and are closely associated with metabolic diseases, such as abnormal glucose and lipid metabolism and diabetes. Previous studies have demonstrated that CTRPs are highly involved in the regulation of numerous physiological and pathological processes, including glycolipid metabolism, protein kinase pathways, cell proliferation, cell apoptosis and inflammation. CTRPs also play important roles in the development and progression of numerous types of tumor, including liver, colon and lung cancers. This observation can be attributed to the fact that diabetes, obesity and insulin resistance are independent risk factors for tumorigenesis. Numerous CTRPs, including CTRP3, CTRP4, CTRP6 and CTRP8, have been reported to be associated with tumor progression by activating multiple signal pathways. CTRPs could therefore be considered as diagnostic markers and therapeutic targets in some cancers. However, the underlying mechanisms of CTRPs in tumorigenesis remain unknown. The present review aimed to determine the roles and underlying mechanisms of CTRPs in tumorigenesis, which may help the development of novel cancer treatments in the future.

CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR‐424‐5p/FoxO1 pathway in THP‐1 macrophage‐derived foam cells

Prevention of ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux leads to lipid accumulation in macrophages and atherosclerosis development. C1q tumor necrosis factor-related protein 1 (CTRP1), a conserved paralog of adiponectin, has been shown to aggravate atherosclerosis via its proinflammatory property. However, very little is known about its effects on ABCA1 expression and macrophage lipid accumulation. In the current studies, we found that CTRP1 downregulated ABCA1 expression, inhibited cholesterol efflux to apoA-I and promoted lipid accumulation in THP-1 macrophage-derived foam cells. Forkhead box O1 (FoxO1), a transcriptional repressor of ABCA1, was identified as a direct target of miR-424-5p. Mechanistically, CTRP1 attenuated miR-424-5p levels and then augmented FoxO1 expression in the nucleus, which led to downregulation of ABCA1 expression and inhibition of cholesterol efflux. In conclusion, these findings suggest that CTRP1 restrains cholesterol efflux and facilitates macrophage lipid accumulation through the miR-424-5p/FoxO1/ABCA1 signaling pathway, thereby providing a novel mechanistical insight into its proatherosclerotic action.

Association between serum CTRP9 levels and diabetic retinopathy in patients with type 2 diabetes mellitus

To investigate the relationship between serum C1q tumor necrosis factor-related protein 9 (CTRP9) level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 291 patients with T2DM underwent fundus examination, and their serum levels of CTRP9, insulin and adiponectin were measured using enzyme- linked immunosorbent assay. According to results of fundus examination, the patients were divided into DR group and non-DR (NDR) group, and logistic regression was used to analyze the relationship between serum CTRP9 levels and DR in T2DM patients. Compared with those in NDR group, the patients with DR showed significantly increased serum CTRP9 level (P < 0.001) and decreased serum adiponectin level (P < 0.001). Pearson correlation analysis showed that in patients with T2DM complicated by DR, serum CTRP9 levels had a significant positive correlation with DR stage (P < 0.05) and a negative correlation with serum adiponectin level (P < 0.001). Multivariate logistic regression analysis showed that with the increase of serum CTRP9 level, the risk of DR is significantly increased in patients with T2DM. In patients with T2DM complicated by DR, an increased serum CTRP9 level suggests a compensatory response to DR.

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXR\u03b1 pathway

C1q tumor necrosis factor-related protein 12 (CTRP12), a conserved paralog of adiponectin, is closely associated with cardiovascular disease. However, little is known about its role in atherogenesis. The aim of this study was to examine the influence of CTRP12 on atherosclerosis and explore the underlying mechanisms. Our results showed that lentivirus-mediated CTRP12 overexpression inhibited lipid accumulation and inflammatory response in lipid-laden macrophages. Mechanistically, CTRP12 decreased miR-155-5p levels and then increased its target gene liver X receptor α (LXRα) expression, which increased ATP binding cassette transporter A1 (ABCA1)- and ABCG1-dependent cholesterol efflux and promoted macrophage polarization to the M2 phenotype. Injection of lentiviral vector expressing CTRP12 decreased atherosclerotic lesion area, elevated plasma high-density lipoprotein cholesterol levels, promoted reverse cholesterol transport (RCT), and alleviated inflammatory response in apolipoprotein E-deficient (apoE−/−) mice fed a Western diet. Similar to the findings of in vitro experiments, CTRP12 overexpression diminished miR-155-5p levels but increased LXRα, ABCA1, and ABCG1 expression in the aortas of apoE−/− mice. Taken together, these results suggest that CTRP12 protects against atherosclerosis by enhancing RCT efficiency and mitigating vascular inflammation via the miR-155-5p/LXRα pathway. Stimulating CTRP12 production could be a novel approach for reducing atherosclerosis.

Association of serum CTRP9 levels with cardiac autonomic neuropathy in patients with type 2 diabetes mellitus.

AimsCardiac autonomic neuropathy (CAN) is a serious complication of diabetes and is associated with adipokines. The C1q tumor necrosis factor‐related protein 9 (CTRP9) is a newly discovered adipokine. This study aimed to evaluate the association of serum CTRP9 levels with the prevalence and severity of CAN in patients with type 2 diabetes mellitus.Materials and MethodsWe enrolled 262 patients (aged ≥18 years) with type 2 diabetes mellitus into this study. Standard cardiovascular autonomic reflex tests (CARTs) were used to assess CAN and patients were divided into three groups accordingly: a non‐CAN group, an early CAN group, and a definite CAN group. Serum CTRP9 levels were measured by enzyme‐linked immunosorbent assay, and the tertiles were calculated.ResultsSerum CTRP9 levels decreased significantly in the early CAN and definite CAN groups (P < 0.05). The percentage of definite CAN was the highest at the minimum tertile of serum CTRP9 level (T1; P < 0.05). Additionally, serum CTRP9 levels were negatively correlated with age, DM duration, hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) while positively correlated with high‐density lipoprotein cholesterol (HDL; P < 0.05). The level of CTRP9 was also significantly associated with the four indexes of CARTs (P < 0.05). Furthermore, CTRP9 was a protective factor for definite CAN (P < 0.05). Compared with the maximum tertile (T3) of the serum CTRP9 levels, a decreased level of serum CTRP9 in T1 significantly increased the prevalence ratio of definite CAN in patients with type 2 diabetes mellitus (P < 0.05).ConclusionSerum CTRP9 levels were independently associated with definite CAN. CTRP9 represents a reliable biomarker for exploring CAN in patients with type 2 diabetes mellitus.

BCL-6 promotes the methylation of miR-34a by recruiting EZH2 and upregulating CTRP9 to protect ischemic myocardial injury.

Acute myocardial infarction (AMI) and the following heart failure are public health problems faced all over the globe. The current study set out to investigate the role of B-cell lymphoma 6 (BCL-6) in cardiac protection after AMI. Initially, AMI mouse models and H9c2 cell oxygen-glucose deprivation (OGD) models were established. The cell models were transfected with the vectors containing oe-BCL-6, oe-EZH2, sh-EZH2, miR-34a mimic, and miR-34a inhibitor. RT-qPCR and Western blot analysis were applied to detect the expression patterns of microRNA-34a (miR-34a), BCL-6, enhancer of zeste homolog 2 (EZH2), and C1q tumor necrosis factor-related protein 9 (CTRP9) in the treated cell models. ChIP-qPCR and co-immunoprecipitation assay were performed to detect EZH2 enrichment and H3K27me3 levels in the miR-34a promoter region and the interaction between BCL-2 and EZH2, respectively. EdU staining, TUNEL staining, and flow cytometry were performed to detect cell proliferation and apoptosis, while ELISA was conducted to detect the oxidative stress levels. It was found that miR-34a was highly expressed in heart tissues of AMI models, while BCL-6 and EZH2 were poorly expressed. BCL-2 overexpression increased the recruitment of EZH2, upregulated H3K27me3 level in the miR-34a promoter region, and inhibited the miR-34a expression. Ctrp9, the downstream negative-regulatory molecule of miR-34a, was upregulated. Besides, miR-34a/CTRP9 expression changes were found to affect cardiomyocyte apoptosis, oxidation stress, and proliferation, and prevent myocardial injury in AMI mice. Our findings indicate that BCL-6 increases the level of H3K27me3 in the promoter region of miR-34a via EZH2 recruitment and CTRP9 upregulation, which inhibits the apoptosis of myocardial cells.

C1QTNF6 regulates cell proliferation and apoptosis of NSCLC in vitro and in vivo.

Objectives: Lung cancer has been reported as the leading cause of cancer-associated deaths in humans, and its incidence continues to increase in the world. A growing number of studies have shown that dysregulated genes are associated with the occurrence and poor prognosis of a variety of tumors, including non-small cell lung cancer (NSCLC). C1q/tumor necrosis factor-related protein 6 (C1QTNF6), a member of the C1q/tumor necrosis factor-related protein (CTRP) family, has been revealed to play a role in carcinogenesis and cancer progression. Nevertheless, the effects and mechanisms of C1QTNF6 in NSCLC remain unrevealed. Materials and methods: MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide) and colony formation, flow cytometric and transwell assays were performed to explore the cell function. Real-time PCR (RT-PCR) and Western blot were used to analyze the mRNA and protein expression. Results: In the present study, we found that C1QTNF6 significantly promoted the proliferation of SPCA1 and A549 cells by MTT and colony formation assays. In addition, down-regulation of C1QTNF6 weakened the tumor growth in vivo. Besides, C1QTNF6 remarkably reduced apoptosis by flow cytometric analysis and TUNEL assay. Furthermore, the capability of migration and invasion was obviously enhanced on C1QTNF6 overexpression. Conclusion: Overall, our results demonstrated that inhibition of C1QTNF6 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and in vivo of NSCLC. Based on the above results, our study provided us with a new and key perspective in understanding and treating NSCLC.

Association of Plasma C1q/TNF-Related Protein 3 (CTRP3) in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia characterized by atrial remodeling. Complement C1q tumor necrosis factor-related protein 3 (CTRP3) is one of the adipokines associated with obesity, diabetes, and coronary heart disease. The association between plasma CTRP3 levels and AF is uncertain. The aim of this study was to investigate whether plasma CTRP3 concentrations were correlated with AF. Our study included 75 AF patients who underwent catheter ablation at our hospital and 47 sinus rhythm patients to determine the difference in plasma CTRP3 concentrations. Blood samples before the ablation were collected, and ELISA was used to measure the concentrations of CTRP3. Plasma CTRP3 concentrations were significantly lower in AF patients compared with control group (366.9 ± 105.2 ng/ml vs. 429.1 ± 100.1 ng/ml, p = 0.002). In subgroup studies, patients with persistent AF had lower plasma CTRP3 concentrations than those with paroxysmal AF (328.3 ± 83.3 ng/ml vs. 380.0 ± 109.2 ng/ml, p = 0.037). The concentrations of plasma CTRP3 in the recurrence group after radiofrequency catheter ablation of AF were lower than those in the nonrecurrence group (337.9 ± 77.3 ng/ml vs. 386.6 ± 108.1 ng/ml, p = 0.045). Multivariate regression analysis revealed the independent correlation between plasma CTRP3 level and AF. Plasma CTRP3 concentrations were correlated with the presence of AF and AF recurrence.

New Insights Into Implications of CTRP3 in Obesity, Metabolic Dysfunction, and Cardiovascular Diseases: Potential of Therapeutic Interventions.

Adipose tissue, as the largest endocrine organ, secretes many biologically active molecules circulating in the bloodstream, collectively termed adipocytokines, which not only regulate the metabolism but also play a role in pathophysiological processes. C1q tumor necrosis factor (TNF)-related protein 3 (CTRP3) is a member of C1q tumor necrosis factor-related proteins (CTRPs), which is a paralog of adiponectin. CTRP3 has a wide range of effects on glucose/lipid metabolism, inflammation, and contributes to cardiovascular protection. In this review, we comprehensively discussed the latest research on CTRP3 in obesity, diabetes, metabolic syndrome, and cardiovascular diseases.

Correlation of serum C1q-tumour necrosis factor-related protein 5 levels with metabolic parameters and carotid intima-media thickness in newly diagnosed type 2 diabetes mellitus patients.

Recent studies have shown that cytokines secreted from adipose tissues play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). CTRP5 (C1q-TNF-related protein 5) is a novel adipokine that has been shown to be associated with glucose and lipid metabolism. Varying levels of CTRP5 have been reported in individuals with diabetes, obesity and coronary artery disease. The aim of this study was to examine serum levels of CTRP5 and to show the relationship with cardiometabolic parameters in T2DM patients. The study included 40 T2DM patients and 40 age- and sex-matched healthy control subjects. All the study participants were evaluated with respect to BMI, waist circumference, lipid profile, insulin resistance (HOMA-IR), serum CTRP5 levels, carotid intima-media thickness, and hs-CRP. No statistically significant differences were found between the control group and the diabetic group in terms of age, sex, or BMI. Serum CTRP5 levels (T2DM = 94.55 ± 28.70ng/ml, control = 76.02 ± 27.22ng/ml, P = 0.004*) were significantly higher in the group of newly diagnosed diabetic patients. A positive correlation was found between CTRP5 and the cardiometabolic parameters of carotid intima-media thickness (CIMT), hs-CRP, HOMA-IR and BMI. Regression analysis results showed that CTRP5 levels were independently correlated with insulin resistance estimated by HOMA-IR. Serum CTRP5 levels were correlated with cardiometabolic parameters and could therefore be a promising indicator of metabolic status and a possible biomarker of insulin resistance. However, the contradictory results reported in different studies indicate the need for further research to assess the significance of CTRP5 for diagnosis and monitoring of treatment efficacy.

C1q/TNF-related protein-9 alleviates airway inflammation in asthma

BackgroundsAsthma is characterized as inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of childhood asthma is necessary. Here, we conducted the present study to investigate the effects of CTRP9 (C1q tumor necrosis factor-related protein 9), a newly identified anti-inflammatory factor, on asthma. MethodsSixty asthmatic children (30 moderate and 30 mild) were recruited. The mRNA level of CTRP9 in peripheral blood mononuclear cells (PBMCs) and protein level of CTRP9 in serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA, respectively. The anti-inflammatory effects of CTRP9 was determined in vitro and potential therapeutic effect on asthma was evaluated in mouse model. ResultsThe mRNA and protein levels of CTRP9 was significantly down-regulated in asthmatics than HCs. Furthermore, the expression level of CTRP9 was negatively correlated with the expression of TNF-α, IL-1β, and IL-6 in PBMCs. The CTRP9 significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering CTRP9 into mouse model of asthma showed disease alleviation. ConclusionOur data here indicated that CTRP9 may alleviate airway inflammation and remodeling in asthma.

MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway.

Inflammatory responses are considered to be the critical mechanism underlying particulate matter (PM)-induced development and exacerbation of chronic respiratory diseases. MiR-29b-3p has been found to participate in various biological processes, but its role in PM-induced inflammatory responses was previously unknown. Here, we constructed a miRNA PCR array to find that miR-29b-3p was the most highly expressed in human bronchial epithelial cells (HBECs) exposed to PM. MiR-29b-3p promoted PM-induced pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) expression via inhibiting the AMPK signaling pathway in HBECs. RNA sequencing and luciferase reporter assay identified that miR-29b-3p targeted complement C1q tumor necrosis factor-related protein 6 (C1QTNF6), a protein that protected from PM-induced inflammatory responses via activating the AMPK signaling pathway. In vivo, miR-29b-3p antagomirs delivered via the tail vein prior to PM exposure significantly counteracted PM-induced miR-29b-3p upregulation and C1QTNF6 downregulation in lung tissues. Furthermore, miR-29b-3p inhibition alleviated inflammatory cells infiltration and pro-inflammatory cytokines secretion in the lung of PM-exposed mice. These findings firstly revealed that miR-29b-3p acted as a novel modulator of PM-induced inflammatory responses by targeting the C1QTNF6/AMPK signaling pathway, which contributes to a better understanding of the biological mechanisms underlying adverse PM-induced respiratory health effects.

Circulating CTRP1 Levels Are Increased and Associated with the STOD in Essential Hypertension in Chinese Patients.

This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 patients complicated with STOD and 177 patients without STOD. In the STOD group, there were 87 patients with left ventricular hypertrophy (LVH), 32 patients with microalbuminuria (MAU), and 58 patients with complication of LVH and MAU. Enzyme-linked immunosorbent assay (ELISA) was used to detect the CTRP1, adiponectin (APN), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). We found that CTRP1 levels were higher in patients with EH than those in healthy subjects; moreover, the level of CTRP1 of patients in the group complicated with EH and STOD was increased compared with EH patients without STOD. CTRP1 levels in the group complicated with LVH and MAU were significantly higher than those in the LVH group and the MAU group. Furthermore, APN, CTRP1, and IL-6 were three factors that influenced the STOD of EH patients, among which CTRP1 and IL6 were positively related with the complication of hypertension and STOD. In conclusion, CTRP1 levels are increased and associated with the STOD (heart and kidney) in essential hypertension, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension.

Association of C1q/TNF-related protein-1 (CTRP1) serum levels with coronary artery disease.

ObjectiveComplement C1q tumor necrosis factor-related proteins (CTRPs), belonging to the CTRP superfamily, are extensively involved in regulating metabolism and the immune-inflammatory response. The inflammatory process is linked to the pathogenesis of coronary artery disease (CAD). Here, we investigated the association of serum levels of CTRP1 with CAD.MethodsStudy participants were divided into two groups according to the results of coronary angiography: a control group (n = 63) and a CAD group (n = 76). The concentrations of serum CTRP1 and inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Further analysis of CTRP1 levels in individuals with different severities of CAD was conducted. The CAD severity was assessed by Gensini score.ResultsSerum levels of CTRP1 were significantly higher in CAD patients than in controls (17.24 ± 1.07 versus 9.31 ± 0.56 ng/mL), and CTRP1 levels increased with increasing severity of CAD. CTRP1 levels were positively correlated with concentrations of tumor necrosis factor-α and interleukin-6. Multiple logistic regression analysis showed that CTRP1 was significantly associated with CAD.ConclusionsOur data showed close associations of serum CTRP1 levels with the prevalence and severity of CAD, indicating that CTRP1 can be regarded as a novel and valuable biomarker for CAD.