Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Pek, Sharon Li Ting; Cheng, Anton; Lin, Michelle Xueqin; Wong, Moh Sim; Chan, Eric Zit Liang; Moh, Angela; Sum, Chee Fang; Lim, Su Chi; Tavintharan, Subramaniam

doi:10.1002/dmrr.3029

Cited by 27 publications

(20 citation statements)

References 38 publications

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“…Therefore, we speculate that Lrg1 has a similar function in AD. It is also reported that the expression level of Lrg1 is correlated with inflammation [62]. Therefore, a significant decrease in the Lrg1 expression level after Se-Met treatment of 3xTg AD mice confirmed that Se-Met has a role in alleviating the inflammation of AD, which agrees with our previous results [9,10].…”

Section: Discussionsupporting

confidence: 91%

Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

Zheng

Zhang

Zhao

et al. 2019

IJMS

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Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by the presence of extracellular senile plaques primarily composed of Aβ peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau proteins. Olfactory dysfunction is an early clinical phenotype in AD and was reported to be attributable to the presence of NFTs, senile Aβ plaques in the olfactory bulb (OB). Our previous research found that selenomethionine (Se-Met), a major form of selenium (Se) in organisms, effectively increased oxidation resistance as well as reduced the generation and deposition of Aβ and tau hyperphosphorylation in the olfactory bulb of a triple transgenic mouse model of AD (3×Tg-AD), thereby suggesting a potential therapeutic option for AD. In this study, we further investigated changes in the transcriptome data of olfactory bulb tissues of 7-month-old triple transgenic AD (3×Tg-AD) mice treated with Se-Met (6 µg/mL) for three months. Comparison of the gene expression profile between Se-Met-treated and control mice revealed 143 differentially expressed genes (DEGs). Among these genes, 21 DEGs were upregulated and 122 downregulated. The DEGs were then annotated against the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The results show that upregulated genes can be roughly classified into three types. Some of them mainly regulate the regeneration of nerves, such as Fabp7, Evt5 and Gal; some are involved in improving cognition and memory, such as Areg; and some are involved in anti-oxidative stress and anti-apoptosis, such as Adcyap1 and Scg2. The downregulated genes are mainly associated with inflammation and apoptosis, such as Lrg1, Scgb3a1 and Pglyrp1. The reliability of the transcriptomic data was validated by quantitative real time polymerase chain reaction (qRT-PCR) for the selected genes. These results were in line with our previous study, which indicated therapeutic effects of Se-Met on AD mice, providing a theoretical basis for further study of the treatment of AD by Se-Met.

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Section: Discussionsupporting

confidence: 91%

Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

Zheng

Zhang

Zhao

et al. 2019

IJMS

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“…This suggests a potential mechanistic link between LRG1, inflammation and atherosclerosis in this patient population, and broadens the role of LRG1 in diseases characterized by chronic inflammation. An increased LRG1 level has been observed in obese and morbidly obese subjects and is associated with a higher hsCRP level 23 . While there was no correlation between LRG1 titer and weight or lipid profile in our study, LRG1 was significantly linked with systemic inflammation and enhanced T cell differentiation.…”

Section: Discussionmentioning

confidence: 97%

Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Cardiovascular Disease Risk in End-Stage Renal Disease

Yang

Hsieh

Shu

et al. 2020

Sci Rep

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plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD. Cardiovascular mortality in patients with end-stage renal disease (ESRD) remains the leading cause of death 1,2. These patients exhibit a strikingly higher risk (20-400 folds) of cardiovascular mortality compared to age-matched health subjects without any kidney disease 3. Traditional risk factors as well as non-traditional risk factors, such as inflammation, are believed to contribute to the excessively heavy burden of cardiovascular disease in chronic kidney disease (CKD) and ESRD patients 3. The pro-inflammatory microenvironment is collectively caused by uremic milieu, infection, and tissue ischemia even before the initiation of dialysis 4. Innate immunity is the evolutionarily conserved host response mediated by pattern recognition receptors (PRRs), which bind endogenous or exogenous ligands and initiate downstream signaling pathways to establish an immediate responses as the first line of defense. Two types of PRRs, Toll-like receptors (TLRs) over the cell surface and inflammasomes in the cytoplasm can interact with endogenous ligands. They are involved in the development of pro-inflammatory microenvironment in renal failure. Activation of these innate immune pathways is

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“…Subsequent studies from our group and others have shown that LRG is increased in various immune-related diseases such as adult-onset Still's disease 19 , psoriasis 20 , juvenile idiopathic arthritis 21 , Kawasaki disease 22 , appendicitis 23 and cancers 24,25 , indicating that LRG elevation is not limited to autoimmune diseases. In addition, LRG may serve as a biomarker for several other disease conditions such as heart failure 26 , diabetes-related complications [27][28][29] and obesity 30 , which are not typical inflammatory www.nature.com/scientificreports www.nature.com/scientificreports/ diseases but may involve immunopathogenic mechanisms. Thus, for diagnosis of active TB, LRG should be used in conjunction with other laboratory tests such as IGRA.…”

Section: Discussionmentioning

confidence: 99%

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Fujimoto

Matsumoto

Serada

et al. 2020

Sci Rep

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB. Tuberculosis (TB) is a symptomatic disease caused by replicating Mycobacterium tuberculosis (Mtb). According to the WHO global tuberculosis report 2018 (https://www.who.int/tb/publications/global_report/en/), about 23% of the world's population is estimated to be latently infected with Mtb, Of these, up to 10% of humans develop active disease after Mtb infection 1 , which makes TB a major global health problem with the estimation of 10.4 million new cases and 1.7 million deaths in 2016 2. Importantly, 40% of estimated TB cases remain to be undiagnosed 2. Rapid detection of active TB is critical to reduce TB-related death. Recently-introduced interferon gamma release assay (IGRA) has better specificity than tuberculin skin test (TST) in TB screening and now become the standard for the identification of Mtb sensitization 1. Nevertheless, IGRA does not differentiate between active TB and resolved/latent infection 3. At present, sputum smear or culture of Mtb is still a gold standard for diagnosis of active TB. In addition, sputum culture is also a major biomarker for the evaluation of treatment 1,4,5. However, sputum test is assessable only when sputa of good quality were obtained from patients. Accordingly, sputum test is unavailable for infants with TB and patients with extrapulmonary tuberculosis. In addition, sputum test is not always available in resource-poor settings. Moreover, the sputum culture is not suitable for rapid decision making during therapy of outpatients, given that it requires long time before obtaining results 1. To detect Mtb in sputa in a rapid turnaround time, molecular diagnostics such as the GeneXpert MTB/RIF assay may be applicable 5. Nevertheless, this assay is ex...

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Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Cited by 27 publications

References 38 publications

Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Cardiovascular Disease Risk in End-Stage Renal Disease

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

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