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. 2020 Apr 6;21(1):122.
doi: 10.1186/s12882-020-01782-0.

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

Yi Yang  1 , Ran Luo  1 , Yichun Cheng  1 , Tingting Liu  1 , Wei Dai  1 , Yueqiang Li  1 , Shuwang Ge  2 , Gang Xu  1
Affiliations

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

Yi Yang et al. BMC Nephrol. .

Abstract

Background: Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases VSports手机版. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). .

Methods: Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1 V体育安卓版. .

Results: We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines V体育ios版. .

Conclusions: Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients VSports最新版本. .

Keywords: Apoptosis; Inflammation; Leucine-rich α2-glycoprotein-1; Lupus nephritis; Proliferation V体育平台登录. .

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The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Plasma leucine-rich alpha-2 glycoprotein 1 (LRG1) levels in lupus nephritis (LN) patients and its correlation to indicators. a Plasma LRG1 levels in LN patients and healthy controls. b Differences in plasma concentrations of LRG1 between different patients with different CKD grades. c Plasma levels of LRG1 are positively correlated with serum creatinine (γ = 0.294, P < 0.01). d, e Differences in plasma concentrations of LRG1 between different patients with different SLE activity grade (SLEDAI) and renal SLEDAI (rSLEDAI). f Differences in plasma concentrations of LRG1 between different patients with other different clinical and pathological indicators, 1 and 2 are representative < and ≥ median: 29.0 years for age, 5.0 AI score, 4.0 CI score, 0.4 for complement 3 (C3); female and male for gender; < and ≥ 20 for SLEDAI;<20 and ≥ 20 mm/h for erythrocyte sedimentation rate (ESR); − and + for hematuria, heavy proteinuria, pyuria, casts, double track sign, wireloop sign, endothelial cells hyperplasia and fibrosis; light and heavy for inflammatory cell infiltration. Symbols represent individual data points with the median as a horizontal line in Fig. 1a, b, d and e. Data are presented as bar graphs with the median and 25–75th percentile of the plasma LRG1 concentrations in Fig. 1f (ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001)
Fig. 2
Fig. 2
Flow cytometric analysis of leucine-rich alpha-2 glycoprotein 1 (LRG1) expression in peripheral blood leukocytes of LN patients and HC. Quantitative presentations of LRG1+ cells in CD15+ (Neutrophils), CD3-CD 56+ (NK cells), CD14+ (Monocytes), CD3+ (T cells) and CD19+ (B cells) cells for healthy controls and lupus nephritis (LN) patients. n = 3 per group. ns, not significant; *P < 0.05; ***P < 0.001
Fig. 3
Fig. 3
Renal cortical expression of leucine-rich alpha-2 glycoprotein 1 (LRG1) in human kidney biopsies. Representative photomicrographs of LRG1 staining in human renal cortical tissue from normal subjects (a and b), lupus nephritis (LN) patients (c and d). Hematoxylin stain; original magnification, × 200 (A and C, Scale bars, 50 μm); × 400 (b and d, Scale bars, 20 μm)
Fig. 4
Fig. 4
Leucine-rich alpha-2 glycoprotein 1 (LRG1) was expressed at proximal tubules and several inflammatory cells in kidneys of lupus nephritis (LN) patients. a Continuous kidney paraffin sections of LN patients were co-stained with anti-LRG1 and anti- Lotus tetragonolobus lectin (LTL)/Nacl cotransporter (NCC)/Dolichos biflorus agglutinin (DBA) antibodies. Representative images of the border areas are shown. Scale bars, 100 μm. b Paraffin sections of LN patients were co-stained with anti-LRG1 and anti-68/11c/3/19 antibodies. Representative images of the border areas are shown. Scale bars, 20 μm
Fig. 5
Fig. 5
Leucine-rich alpha-2 glycoprotein 1 (LRG1) could be induced by proinflammatory cytokines in HK-2 cell line and its effects on HUVEC cell line. a, b The expressions of LRG1 were analysed by western blot in HK-2 cells stimulated with 20 ng/mL IL-1β, IL-6, TNF-α and INF-γ for 8 h (n = 3). Analyses were performed by Student’s t test. c HUVEC cells stimulated by 500 ng/mL rhLRG1 for 8 h were double stained with FITC-conjugated anti-Annexin Vantibody and PI, followed by flowcytometry analysis for cell apoptosis. d CCK-8 assay was performed to assess cell proliferation in HUVEC cell line. e HUVEC cell line was stimulated by 500 ng/mL rhLRG1 for 24 h. The expression of mRNA was analyzed by real-time RT-PCR and GAPDH was used as an internal control for grayscale analysis. Data are shown as mean ± SEM. c-e analyses were controls groups vs. 500 ng/mL LRG1 stimulating groups performed by Student’s t test. n.s., not significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. LRG1: leucine-rich α2-glycoprotein 1; IL: Interleukin; TNF: Tumor necrosis factor; INF: Interferon; CCL: chemokine (C-C motif) ligand; CXCL: Chemokine (C-X-C Motif) Ligand 1
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