scholarly journals Macroglobulin signaling system

2012 ◽  
Vol 58 (4) ◽  
pp. 400-410
Author(s):  
N.A. Zorin ◽  
V.N. Zorina

This review will focus on the systematization of knowledge about structure of macroglobulin signaling system, which includes macroglobulin family proteins (alpha-2-macroglobulin, alpha-2-glycoprotein, pregnancy associated plasma protein A), their receptors (LRP, grp78), ligands (proteinases, cytokines, hormones, lipids, et al.) transforming and transcriptional factors for regulation of macroglobulins synthesis. After reviewing the functions of macroglobulin signaling system, and mechanisms of their realization, we discuss the complex and significant role of this system in different physiological and pathological processes.

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Weiping Li ◽  
Hongwei Li ◽  
Li Zhou ◽  
Zijian Wang ◽  
Bing Hua

Pregnancy-associated plasma protein A (PAPP-A) was previously reported to be an inflammatory biomarker and a prognostic marker of acute coronary syndrome (ACS) and involved in the process of atherosclerosis and plaque rupture. However, the role of PAPP-A in inflammation is poorly understood. In this study, we aimed to investigate the role of PAPP-A in macrophage activation and inflammatory cytokine production. RAW264.7 macrophages were treated with or without PAPP-A. Reverse-transcriptase quantitative real-time PCR (RT-qPCR) and Western blot were performed to detect gene and protein expressions. The concentration of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in culture supernatants was determined by ELISA. Results showed that PAPP-A significantly stimulated the expression of MCP-1, TNF-α, and IL-6 at both transcriptional and translational levels in a dose-dependent and time-dependent manner. The secretion of these inflammatory cytokines by macrophages was also increased after PAPP-A treatment. Moreover, PAPP-A activated the IGF-I/PI3K/Akt signaling pathway in macrophages. The PAPP-A-mediated upregulation of MCP-1, TNF-α, and IL-6 mRNA and protein levels were strongly inhibited by PI3K inhibitors or IGF-IR siRNA, indicating that the upregulation of MCP-1, TNF-α, and IL-6 could involve the IGF-I/PI3K/Akt pathway. Together, this study demonstrates that PAPP-A activates the macrophage signaling pathway (IGF-I/PI3K/Akt), which drives the expression and production of inflammatory cytokines known to contribute to the initiation and progression of ACS. These findings indicate that PAPP-A may play a proinflammatory role in the pathophysiology of ACS and serve as a potential therapeutic target.


Author(s):  
Asmita Kaundal ◽  
Usha Gupta ◽  
Jayashree Bhattcharjee

Background: The study aimed at defining the role of Pregnancy associated plasma protein-A (PAPP-A) and uterine artery doppler (Ut.A.PI) in the development of adverse pregnancy outcome (APO) in high risk pregnancies.Methods: This was an observational study where 100 singleton pregnancies at high risk of development of APO, between 11 to 13 + 6 weeks POG were enrolled. PAPP-A levels were measured at 11 to 13 + 6 weeks POG and uterine artery doppler PI was measured at 20 weeks. Women were followed till delivery. Pregnancy outcome were seen and a cut off at which APO developed was derived.Results: In this study women with lower mean PAPP-A (0.75±0.19 MOM versus 1.23±0.31MOM) (p<0.001) values and higher Ut.A.PI (1.43±0.35MOM versus 0.99±0.25MOM) (p<0.001) developed APO. Cut off value for PAPP-A and Ut.A.PI was determined and was found to be ≤11.65 µg/ml (≤0.79MoM) and   >1.42 (>1.19MoM) respectively which was higher than what is determined in other studies done on low risks populations thereby suggesting for an intervention or more meticulous observations at a higher cut offs.Conclusions: PAPP-A and uterine artery doppler are already being used for the screening of preeclampsia in most of the countries but not for other adverse pregnancy outcomes. PAPP-A levels along with the uterine artery PI in predicting APO in high risk women has high negative predictive value. Hence can be uses as a screening method in high risk population whether they should be used for low risk population also needs further evaluation.


2018 ◽  
Vol 114 (7) ◽  
pp. 992-1005 ◽  
Author(s):  
Lucio Barile ◽  
Elisabetta Cervio ◽  
Vincenzo Lionetti ◽  
Giuseppina Milano ◽  
Alessandra Ciullo ◽  
...  

2013 ◽  
Vol 8 ◽  
Author(s):  
Serdar Berk ◽  
Omer Tamer Dogan ◽  
Eylem Itir Aydemir ◽  
Asli Bingol ◽  
Sefa Levent Ozsahin ◽  
...  

Background: The role of biomarkers for prognostication and diagnosis of pulmonary embolism (PE) is increasing. It has been reported that pregnancy-associated plasma protein-A (PAPP-A) can be used as a proatherosclerotic marker. The present study was aimed to evaluate whether PAPP-A levels are helpful in the differential diagnosis of patients presenting with suspected PE. Methods: 53 consecutive patients evaluated for suspected PE were prospectively enrolled in the study. Serum PAPP-A levels were measured in the blood samples which were taken at admission. Multi-slice computed tomographic angiography was used to verify the diagnosis of PE. Results: PE was detected in 24 out of the 53 patients, while it was excluded in 29 patients by thorax multi-detector computerized tomography scan. No significant difference was detected in mean serum PAPP-A level between groups (5.72 ± 0.31 mg/L vs. 5.67 ± 0.06 mg/L, respectively). Conclusions: Serum PAPP-A level has no role in the evaluation for PE.


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