Expression level of the growth factor progranulin is related with development of systemic lupus erythematosus

Qiu, Feng; Song, Lijun; Ding, Feng; Liu, Huaxiang; Shu, Qiang; Liu, Weiwei; Li, Xingfu

doi:10.1186/1746-1596-8-88

Cited by 29 publications

(20 citation statements)

References 28 publications

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“…Glucocorticoid binds to cytoplasmic glucocorticoid receptors and forms receptor-corticosteroid complex, which translocates to the nucleus and regulates the transcription of target genes [ 36 ]. The present study found that glucocorticoid can affect the serum levels of both pro-inflammatory and anti-inflammatory cytokines, which accords with our previous studies [ 15 , 27 ].…”

Section: Discussionsupporting

confidence: 94%

“…The imbalance of immune system potentially results in the development of autoimmune disorders. It has been reported that multiple cytokines including pro-inflammatory such as IL-6 and IFN-γ [ 15 ] and anti-inflammatory cytokines such as IL-10 [ 26 ] and progranulin protein (PGRN) [ 27 ] and multiple immunocytes such as Treg [ 28 ], Th17 [ 29 ] and B cell [ 30 ] contribute to the pathogenesis of SLE. Our present study finds that apoE is elevated in active SLE patients accompanying the increase of IFN-γ, IL-6 and IL-10 and strongly correlated with IFN-γ, IL-6 and IL-10 serum levels.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, anti-dsDNA antibody plays a crucial role in the pathogenesis of SLE and is believed to be one of the evaluating factors of SLE disease [ 32 ]. It has been reported that both pro-inflammatory and anti-inflammatory cytokines increased accompanying the increase of SLEDAI score and anti-dsDNA antibody in active SLE [ 15 , 27 ]. SLEDAI score and anti-dsDNA antibody are closely related with SLE disease activity and apoE positively correlated with SLEDAI score and anti-dsDNA antibody, which means the aberrant expressions of apoE were related with SLE disease activity.…”

Section: Discussionmentioning

confidence: 99%

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The positive correlations of apolipoprotein E with disease activity and related cytokines in systemic lupus erythematosus

et al. 2013

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BackgroundThe aim of this study is to investigate the expression of apolipoprotein E (apoE) and the relationship between apoE and disease activity of SLE, and the possible effects of glucocorticoid on apoE and other cytokines activities in SLE patients.MethodsForty treatment-naïve SLE patients and forty matched healthy controls were studied. All the SLE patients received prednisone 1 mg/kg/day for 28 consecutive days. The sera levels of apoE and related cytokines were evaluated by ELISA. The expression of apoE mRNA in peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR.ResultsCompared with healthy controls, the relative expression levels of ApoE proteins and sera levels were significantly up-regulated in active SLE patients. ApoE sera concentrations positively correlated with SLEDAI, anti-dsDNA antibody and the related cytokines including IL-6, IFN-γ and IL-10, and uncorrelated with the concentration of total cholesterol (TC) and triglyceride (TG) in SLE patients. After 4 weeks prednisone treatment, the relative mRNA expression of apoE and the serum levels of apoE and related cytokines decreased.ConclusionsApoE correlated with disease activity and related cytokines in SLE patients. Glucocorticoid can down-regulate the expressions of apoE and related cytokines.Virtual slideThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1646714011077325

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The positive correlations of apolipoprotein E with disease activity and related cytokines in systemic lupus erythematosus

et al. 2013

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“…Our results showed a significant difference between the 3 groups with respect to PGRN and IGFBP-2, except for ILGFBP-2, where no significant difference was noted between the CKD and control groups. These findings agreed with the findings of some studies on PGRN [14,34]. Tanaka et al [13] also found higher levels of PGRN in SLE patients than in controls.…”

Section: Discussionsupporting

confidence: 89%

Progranulin and insulin-like Growth Factor Binding Protein-2 as Biomarkers of Disease Activity and Pathological Changes in Lupus Nephritis

et al. 2017

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Background Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease, characterised by the production of auto-antibodies and the formation of immune complexes due to the polyclonal activation of T and B lymphocytes, which results in tissue and organ damage. During inflammation, neutrophils and macrophages release serine proteases to cleave progranulin (PGRN) into granulin, which exerts its pro-inflammatory effects that counteract the anti-inflammatory effects of intact PGRN. It is suggested that insulin-like growth factor binding protein-2 (IGFBP-2) is a dependable biomarker of renal deterioration but it is still unclear if it has high sensitivity and specificity for discriminating SLE-caused kidney disease from other-cause kidney disease.This study aimed to investigate the diagnostic value of PGRN and ILGFBP-2 in patients with lupus nephritis (LN) and the correlation of these biomarkers with disease activity and renal biopsy pathology. Patients and methods Patients with SLE (n=25) and chronic kidney disease (CKD) (n=25), and age- and sex-matched controls (n=25) were enrolled in the study. Serum PGRN and ILGFBP-2 levels were measured for each group. Results Disease duration was 4.78±4.26 years in the SLE patients. The mean SLE Disease Activity Index score was 15.04±7.54. All renal biopsy results were class 2, 3, and 5 with a percentage of 32, 24, and 44% respectively. PGRN and ILGFBP-2 were significantly higher in SLE patients (p<0.001 all) than in the CKD and control groups. All patients with high levels of biomarkers showed higher values of SLE disease activity. No significant difference was noted between active and inactive LN or classes of renal biopsy with PGRN and ILGFBP-2. Conclusion PGRN and ILGFBP-2 are significantly elevated in SLE compared to CKD and the general population and were associated with the SLE Disease Activity Index but not with active LN or classes of renal biopsy.

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“…PGRN associates with some members in the TNF receptor superfamily, including TNFR1, TNFR2 and DR3 [12] , [14] – [16] , and possesses the ability to suppress inflammation in various kinds of conditions [12] , [17] – [23] . The association between PGRN levels and systemic inflammation and autoimmunity has been reported [24] – [28] , for instance, serum levels of PGRN were elevated in systemic lupus erythematosus and related with disease activity [25] . Auto-antibodies against PGRN have also been found in several autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease, and such antibodies promoted a proinflammatory environment in a subgroup of patients [29] – [31] .…”

Section: Introductionmentioning

confidence: 98%

Progranulin Facilitates Conversion and Function of Regulatory T Cells under Inflammatory Conditions

et al. 2014

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The progranulin (PGRN) is known to protect regulatory T cells (Tregs) from a negative regulation by TNF-α, and its levels are elevated in various kinds of autoimmune diseases. Whether PGRN directly regulates the conversion of CD4+CD25-T cells into Foxp3-expressing regulatory T cells (iTreg), and whether PGRN affects the immunosuppressive function of Tregs, however, remain unknown. In this study we provide evidences demonstrating that PGRN is able to stimulate the conversion of CD4+CD25-T cells into iTreg in a dose-dependent manner in vitro. In addition, PGRN showed synergistic effects with TGF-β1 on the induction of iTreg. PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff). In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development. Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2. Collectively, this study reveals that PGRN directly regulates the numbers and function of Tregs under inflammatory conditions, and provides new insight into the immune regulatory mechanism of PGRN in the pathogenesis of inflammatory and immune-related diseases.

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Expression level of the growth factor progranulin is related with development of systemic lupus erythematosus

Cited by 29 publications

References 28 publications

The positive correlations of apolipoprotein E with disease activity and related cytokines in systemic lupus erythematosus

The positive correlations of apolipoprotein E with disease activity and related cytokines in systemic lupus erythematosus

Progranulin and insulin-like Growth Factor Binding Protein-2 as Biomarkers of Disease Activity and Pathological Changes in Lupus Nephritis

Progranulin Facilitates Conversion and Function of Regulatory T Cells under Inflammatory Conditions

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