CRP Stimulates GDF15 Expression in Endothelial Cells through p53

Kim, Yoonseo; Hooten, Nicole Noren; Evans, Michele K.

doi:10.1155/2018/8278039

Cited by 35 publications

(26 citation statements)

References 53 publications

(62 reference statements)

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“…Correlation between MEG3 expression levels and clinical pathology in patients with pituitary adenoma. differentiation factor 15 (27,28). The expression of MEG3 is controlled by epigenetics and abnormal CpG methylation of MEG3 occurs in various types of tumor, such as cervical cancer and pituitary adenoma (23,29,30).…”

Section: Discussionmentioning

confidence: 99%

lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes

Wang

2021

Oncol Rep

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Pituitary tumors do not pose a threat to life but can cause visual disturbances and serious clinical syndromes, such as infertility and metabolic syndrome. Therefore, screening of key genes involved in the occurrence and development of pituitary tumors can provide new targets for the treatment of pituitary tumors. The aim of the present study was to investigate the molecular mechanism of long non-coding (lnc.) RNA maternally expressed 3 (MEG3) in cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) processes of pituitary tumor. Tissue samples were obtained from 34 patients who underwent surgical treatment of pituitary tumors. Pituitary tumor cells (GH3 and MMQ) were transfected with pcDNA3.1(+)-MEG3, short hairpin (sh)MEG3, microRNA (miR)-23-3p inhibitor or their controls using Lipofectamine ® 2000. Reverse transcription-quantitative PCR and western blot analyses were used to detect the levels of MEG3, miR-23b-3p and FOXO4, as well as proliferation-, apoptosis-and EMT-associated genes and proteins. Cell Counting Kit-8 and flow cytometry assays were performed to detect proliferation and apoptosis, and Transwell assay was undertaken to assess invasion and migration. Luciferase reporter and RNA pulldown assays were performed to verify the binding between lncRNA MEG3, miR-23b-3p and FOXO4. Pearson's correlation analysis was used to analyze the correlation between expression levels of MEG3, miR-23b-3p and FOXO4. lncRNA MEG3 was expressed at lower levels in pituitary tumor tissues and cells. Overexpression of lncRNA MEG3 inhibited proliferation, invasion and migration and accelerated apoptosis of pituitary tumor cells. lncRNA MEG3 negatively regulated miR-23b-3p expression levels, while miR-23b-3p negatively regulated FOXO4 expression levels. Overexpression of lncRNA MEG3 inhibited the EMT process in pituitary tumor cells. miR-23-3p inhibitor rescued the effect of shMEG3 on proliferation, invasion, migration, apoptosis and the EMT process in pituitary tumor cells. lncRNA MEG3 inhibited pituitary tumor development by participating in cell proliferation, apoptosis and the EMT process, which may present a novel target for pituitary tumor treatment.

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Section: Discussionmentioning

confidence: 99%

lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes

Wang

2021

Oncol Rep

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“…Circulating Growth-and-Differentiation Factor 15 (GDF15) can reduce appetite 3 via specific receptors in the area postrema and nucleus tractus solitarius of the brainstem 4 . In the absence of acute illness, C-reactive protein (CRP) and insulin are among the endogenous GDF15 secretagogues, respectively in endothelial cells 5 and in the liver 6 . Metformin is an exogenous GDF15 secretagogue 7 – 9 , whose principal site of GDF15-releasing action is currently thought to be in the gut, in particular in the colon 10 .…”

Section: Introductionmentioning

confidence: 99%

The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat

Zegher

Díaz

Villarroya

et al. 2021

Sci Rep

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A prime concern of young patients with Polycystic Ovary Syndrome (PCOS) is the control of body adiposity, given their tendency to gain weight and/or their difficulty to lose weight. Circulating growth-and-differentiation factor-15 (GDF15) facilitates the control of body weight via receptors in the brainstem. C-reactive protein (CRP) and insulin are endogenous GDF15 secretagogues. We hypothesised that PCOS in non-obese adolescents is characterised by low concentrations of circulating GDF15, when judged by the degree of CRP and insulin drive. GDF15 was added as a post-hoc endpoint of two previously reported, randomised studies in non-obese adolescent girls with PCOS (N = 58; 60% normal weight; 40% overweight) who received either an oral oestroprogestogen contraceptive (OC), or a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET) for 1 year; subsequently, all girls remained untreated for 1 year. Adolescent girls with regular menses (N = 20) served as healthy controls. Circulating GDF15, CRP and fasting insulin were assessed prior to treatment, and halfway the on- and post-treatment years. Pre-treatment, the absolute GDF15 concentrations were normal in PCOS girls, but their relative levels were markedly low, in view of the augmented CRP and insulin drives. OC treatment was accompanied by a near-doubling of circulating GDF15 (on average, from 296 to 507 pg/mL) and CRP, so that the relative GDF15 levels remained low. SPIOMET treatment was accompanied by a 3.4-fold rise of circulating GDF15 (on average, from 308 to 1045 pg/mL) and by a concomitant lowering of CRP and insulin concentrations towards normal, so that the relative GDF15 levels became markedly abundant. Post-OC, the relatively low GDF15 levels persisted; post-SPIOMET, the circulating concentrations of GDF15, CRP and insulin were all normal. BMI remained stable in both treatment groups. Only SPIOMET was accompanied by a reduction of hepato-visceral fat (by MRI) towards normal. In conclusion, early PCOS was found to be characterised by a relative GDF15 deficit that may partly explain the difficulties that young patients experience to control their body adiposity. This relative GDF15 deficit persisted during and after OC treatment. In contrast, SPIOMET treatment was accompanied by an absolute and a relative abundance of GDF15, and followed by normal GDF15, CRP and insulin concentrations. The present findings strengthen the rationale to raise the concentrations of circulating GDF15 in early PCOS, for example with a SPIOMET-like intervention that attenuates low-grade inflammation, insulin resistance and ectopic adiposity, without necessarily lowering body weight.Clinical trial registries: ISRCTN29234515 and ISRCTN11062950.

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“…In vitro, Kim et al reported that the positive correlation between GDF-15 and C-reaction protein in a molecular level, which facilitated improved understanding of the pivotal inflammatory pathways important in CAD [20]. A recently published study observed an association of higher GDF-15 concentration with risk for mortality and heart failure in patients with CKD [21].…”

Section: Discussionmentioning

confidence: 99%

Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

Liu

Lyu

et al. 2019

Cardiovasc Diabetol

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Background There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients. Methods GDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured. Results Serum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower ( p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 ( p < 0.001). In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI). Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD. Conclusions In male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD. Electronic supplementary material The online version of this article (10.1186/s12933-019-0823-3) contains supplementary material, which is available to authorized users.

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CRP Stimulates GDF15 Expression in Endothelial Cells through p53

Cited by 35 publications

References 53 publications

lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes

lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes

The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat

Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

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