A Solid-Phase Assay for Studying Direct Binding of Progranulin to TNFR and Progranulin Antagonism of TNF/TNFR Interactions

Tian, Qingyun; Zhao, Suisheng; Liu, Chuanju

doi:10.1007/978-1-4939-0669-7_14

Cited by 24 publications

(28 citation statements)

References 28 publications

(25 reference statements)

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“…51,60 Deletion mutants of TNFR1 and TNFR2 used to map the binding of PGRN revealed that CRD2 and CRD3 of TNFR are essential for the interaction with PGRN, similar to the binding to TNFa. 55,56,61,62 In conclusion, our present study revealed that administration of PGRN attenuated insulin signaling and triggered ER stress in vivo and in vitro studies, with such effects being drastically reversed by PBA, suggesting a causative role of ER stress in PGRN-induced impaired insulin sensitivity and implicated that decreasing PGRN levels by influencing its turnover or production is consequently a promising therapeutic approach applied to metabolic disorders.…”

Section: Discussionsupporting

confidence: 53%

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Zhou

Liu

et al. 2015

Cell Cycle

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Progranulin (PGRN) has recently emerged as an important regulator for glucose metabolism and insulin sensitivity. However, the direct effects of PGRN in vivo and the underlying mechanisms between PGRN and impaired insulin sensitivity are not fully understood. In this study, mice treated with PGRN for 21 d exhibited the impaired glucose tolerance and insulin sensitivity, remarkable ER stress as well as attenuated insulin signaling in liver and adipose tissue but not in skeletal muscle. Furthermore, treatment of mice with phenyl butyric acid (PBA), a chemical chaperone alleviating ER stress, resulted in a significant restoration of systemic insulin sensitivity and recovery of insulin signaling induced by PGRN. Consistent with these findings in vivo, we also observed that PGRN treatment induced ER stress, impaired insulin signaling in cultured hepatocytes and adipocytes, with such effects being partially nullified by blockade of PERK. Whereas PGRN-deficient hepatocytes and adipocytes were more refractory to palmitate-induced insulin resistance, indicating the causative role of the PERK-eIF2a axis of the ER stress response in action of PGRN. Collectively, our findings supported the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing ER stress via the PERK-eIF2a dependent pathway.

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Section: Discussionsupporting

confidence: 53%

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Zhou

Liu

et al. 2015

Cell Cycle

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“…CTRP‐3 is an adipokine involved in adipogenesis and as a pleiotropic factor in metabolic and immunological processes which has been described to be inversely associated with BMI and metabolic syndrome . Further being well‐known for its anti‐inflammatory properties, CTRP‐3 thus resembles progranulin which has been described as an anti‐atherosclerotic factor and as an inhibitor of pro‐inflammatory TNF signalling . Similar to a potential inhibition of TNF‐induced pro‐inflammatory signalling by progranulin, CTRP‐3 has been demonstrated to antagonize LPS‐ and TNF‐induced inflammation.…”

Section: Introductionmentioning

confidence: 99%

Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery

Brock

Schmid

Karrasch

et al. 2019

Clinical Endocrinology

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Background Progranulin represents an adipokine putatively mediating insulin resistance and inflammation. Data in humans are sparse, and the source of circulating progranulin in obesity is unknown. Objectives Serum progranulin concentrations and subcutaneous (sc) as well as visceral (vis) adipose tissue (AT) progranulin expression were quantified in a large cohort of patients with obesity undergoing bariatric surgery (BS) (n = 153) or a low‐calorie diet (LCD) (n = 121). Cohorts and methods Paired serum and AT mRNA samples were obtained from patients with severe obesity undergoing BS (ROBS cohort; Research in Obesity and Bariatric Surgery). Serum progranulin was measured by ELISA in both cohorts, and AT mRNA expression was analysed by quantitative real‐time PCR in bariatric patients. Results There was no gender‐specific effect in serum progranulin or AT progranulin expression. Importantly, circulating progranulin was independent from adipose tissue gene expression in paired samples. sc AT progranulin expression was higher than in vis AT (P = 0.027), and there was a positive correlation between sc AT and vis AT gene expression (P < 0.001; r = +0.34). Serum progranulin strongly and rapidly increased after BS within 3 days and remained elevated up to 12 months. Serum progranulin was strongly correlated with serum CTRP‐3 levels. Conclusions The present study provides detailed progranulin gene expression data in sc and vis AT in a large, prospective and observational cohort of patients with severe obesity. Serum progranulin concentrations are not predicted by sc or vis AT progranulin gene expression. Thus, AT seems not to be the main source of circulating progranulin levels in obesity.

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“…also have reported that Il-6 can activate the ERK1/2/RSK1/C/EBPβ pathway and PGRN synthesis as a consequence (21). Furthermore, several studies have shown that PGRN may antagonize TNF-α by the activation of its receptors, therefore PGRN may have some anti-inflammatory properties (22). Studies have also regarded TNF-α as an inhibitor of osteoblast differentiation, as well as an activator of osteoclastogenesis (23).…”

Section: Discussionmentioning

confidence: 99%

Progranulin concentration in relation to bone mineral density among obese individuals

Milajerdi¹,

Maghbooli²,

Mohammadi³

et al. 2018

Archives of Endocrinology and Metabolism

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Objective: Adipose tissue, particularly visceral adipose tissue, secretes a variety of cytokines, among which progranulin is a glycoprotein related to the immune system. Along with other secreted proteins, progranulin may be associated with bone mineral density. The aim of this study was to find out whether there are associations between the progranulin and bone mineral density among obese people. Subjects and methods: This cross-sectional study was conducted on 244 obese participants (aged 22-52). Serum progranulin, high sensitive C-reactive protein, oxidised-low dencity lipoprotein, tumor necrosis factor-α, parathormone, vitamin D, and interleukins of 1 β, 4, 6, 10, 13, and 17 concentrations were measured. Anthropometric measurements, body composition and bone mineral density were also assessed. Results: Serum progranulin was directly associated with interleukin-6 and interleukin-1β, while it had a negative association with interleukin-17 and tumor necrosis factor-α. We also observed a statistically significant direct association between progranulin concentration and visceral fat, abdominal fat, waist, abdominal and hip circumferences, hip T-score, and Z-score and T-score for the lumbar region. A partial correlation test has also shown a significant positive correlation regarding serum progranulin and the hip Z-score. Moreover, progranulin level is inversely associated with ospteopenia (P = 0.04 and CI: 0.17,0.96 ). Conclusion: Our study revealed that central obesity may be related to increased progranulin concentration. In addition, progranulin concentration was directly related to bone formation parameters, which indicates the protective effects of progranulin on bone density. Further studies are needed to clarify the exact mechanisms underlying these associations. Arch Endocrinol Metab. 2018;62(2):179-86

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A Solid-Phase Assay for Studying Direct Binding of Progranulin to TNFR and Progranulin Antagonism of TNF/TNFR Interactions

Cited by 24 publications

References 28 publications

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery

Progranulin concentration in relation to bone mineral density among obese individuals

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