Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection, reflecting viral load

Gong, Yi; Zhan, Tingxi; Zhang, Guozhen; Teng, Bing; Yang, Xiaomin; Wu, Yan; Que, Wenjuan; Yan, Xiaofeng; Liu, Hui; Yu, Zujiang

doi:10.1016/j.cyto.2016.05.026

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…reveals that PGRN mRNA is induced in the lungs of mice after infection with sublethal or lethal doses of H1N1 virus[15]. Recently, researchers have found that circulating PGRN levels in human patients are correlated with human immunodeficiency virus and hepatitis B virus infection[16, 17]. These findings suggest that PGRN plays a crucial role in viral infection.…”

Section: Introductionmentioning

confidence: 99%

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling

Wei¹,

Jiang²,

Sun³

et al. 2019

PLoS Pathog

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Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-κB and IRF3 signaling. Furthermore, we showed that PGRN directly interacted with NF-κB essential modulator (NEMO) via its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that macrophage played a major source of PGRN during influenza virus infection, and PGRN neutralizing antibodies could protect against influenza virus-induced lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway exploited by influenza virus with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of PGRN in innate immunity.

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Section: Introductionmentioning

confidence: 99%

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling

Wei¹,

Jiang²,

Sun³

et al. 2019

PLoS Pathog

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“… 10 , 11 PGRN mediates a variety of biological functions, including host defense, inflammation, and tumorigenesis. 10 , 12 , 13 Cross-sectional studies have shown that serum PGRN levels were increased in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. 12 , 14 Animal experiments confirmed the observation that PGRN was up-regulated in infection models and revealed that PGRN was implicated in host defense against bacterial pneumonia, influenza virus-induced lung injury, and sepsis.…”

Section: Introductionmentioning

confidence: 99%

“… 10 , 12 , 13 Cross-sectional studies have shown that serum PGRN levels were increased in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. 12 , 14 Animal experiments confirmed the observation that PGRN was up-regulated in infection models and revealed that PGRN was implicated in host defense against bacterial pneumonia, influenza virus-induced lung injury, and sepsis. 10 , 11 , 15 However, whether serum PGRN levels are quantitatively elevated in COVID-19 patients remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Yao¹,

Luo²,

Liu³

et al. 2021

JIR

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined. Methods We did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis. Results At baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6–119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8–55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1–1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4–689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P = 0.008) and inversely with sICAM-1 (r= −0.609, P = 0.021) and aspartate aminotransferase levels (r= −0.560, P = 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment. Conclusion The present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.

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“…Exclusion criteria included conditions with previously proposed or documented PGRN‐dependency, as they could affect the results (Table ). Patients diagnosed with chronic hepatitis C were excluded from the study, because we were aware that chronic hepatitis may affect plasma levels of progranulin, as was demonstrated in the course of chronic hepatitis B infection . In our study patients with positive anti‐HCV antibody had no record of chronic hepatitis in medical history.…”

Section: Discussionmentioning

confidence: 99%

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

Kotela

Łęgosz

Sarzyńska

et al. 2018

Clin Exp Pharma Physio

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Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention. K E Y W O R D S haemophilia, haemophilic arthropathy, osteoarthritis, progranulin How to cite this article: Kotela A, Wojdasiewicz P, Łęgosz P, et al. Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy. Clin Exp Pharmacol Physiol.

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Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection, reflecting viral load

Cited by 5 publications

References 25 publications

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

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