The expression and function of Gpnmb in lymphatic endothelial cellsKronk, Solorzano, Robinson
et alGene (2025) 942, 148993
Abstract: The lymphatic system functions in fluid homeostasis, lipid absorption and the modulation of the immune response. The role of Gpnmb (osteoactivin), an established osteoinductive molecule with newly identified anti-inflammatory properties, has not been studied in lymphangiogenesis. Here, we demonstrate that Gpnmb increases lymphatic endothelial cell (LEC) migration and lymphangiogenesis marker gene expression in vitro by enhancing pro-autophagic gene expression, while no changes were observed in cell proliferation or viability. In addition, cellular spreading and cytoskeletal reorganization was not altered following Gpnmb treatment. We show that systemic Gpnmb overexpression in vivo leads to increases in lymphatic tubule number per area. Overall, data presented in this study suggest Gpnmb is a positive modulator of lymphangiogenesis.Copyright © 2024. Published by Elsevier B.V.
Biofluid GPNMB/osteoactivin as a potential biomarker of ageing: A cross-sectional studyLiu, Pang, Zhang
et alHeliyon (2024) 10 (17), e36574
Abstract: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population.We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses.In mice, the Gpnmb mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05).The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.© 2024 The Authors. Published by Elsevier Ltd.
Truncated GPNMB, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric β-amyloid peptide1-42 in primary type 1 microgliaKawahara, Hasegawa, Hasegawa
et alJ Neurochem (2024) 168 (7), 1317-1339
Abstract: Glycoprotein non-metastatic melanoma protein B (GPNMB) is up-regulated in one subtype of microglia (MG) surrounding senile plaque depositions of amyloid-beta (Aβ) peptides. However, whether the microglial GPNMB can recognize the fibrous Aβ peptides as ligands remains unknown. In this study, we report that the truncated form of GPNMB, the antigen for 9F5, serves as a scavenger receptor for oligomeric Aβ1-42 (o-Aβ1-42) in rat primary type 1 MG. 125I-labeled o-Aβ1-42 exhibited specific and saturable endosomal/lysosomal degradation in primary-cultured type 1 MG from GPNMB-expressing wild-type mice, whereas the degradation activity was markedly reduced in cells from Gpnmb-knockout mice. The Gpnmb-siRNA significantly inhibits the degradation of 125I-o-Aβ1-42 by murine microglial MG5 cells. Therefore, GPNMB contributes to mouse MG's o-Aβ1-42 clearance. In rat primary type 1 MG, the cell surface expression of truncated GPNMB was confirmed by a flow cytometric analysis using a previously established 9F5 antibody. 125I-labeled o-Aβ1-42 underwent endosomal/lysosomal degradation by rat primary type 1 MG in a dose-dependent fashion, while the 9F5 antibody inhibited the degradation. The binding of 125I-o-Aβ1-42 to the rat primary type 1 MG was inhibited by 42% by excess unlabeled o-Aβ1-42, and by 52% by the 9F5 antibody. Interestingly, the 125I-o-Aβ1-42 degradations by MG-like cells from human-induced pluripotent stem cells was inhibited by the 9F5 antibody, suggesting that truncated GPNMB also serve as a scavenger receptor for o-Aβ1-42 in human MG. Our study demonstrates that the truncated GPNMB (the antigen for 9F5) binds to oligomeric form of Aβ1-42 and functions as a scavenger receptor on MG, and 9F5 antibody can act as a blocking antibody for the truncated GPNMB.© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Soluble mannose receptor: A potential biomarker in Gaucher diseaseBeaton, Hughes
Eur J Haematol (2024) 112 (5), 794-801
Abstract: Soluble mannose receptor (sMR) relates to mannose receptor expression on macrophages, and is elevated in inflammatory disorders. Gaucher disease (GD) has altered macrophage function and utilises mannose receptors for enzyme replacement therapy (ERT) endocytosis. sMR has not previously been studied in GD.sMR was measured by ELISA and correlated with GD clinical features including spleen and liver volume, haemoglobin and platelet count, bone marrow burden (BMB) scores and immunoglobulin levels. sMR was compared with biomarkers of GD: chitotriosidase, lyso-GL1, PARC, CCL3, CCL4, osteoactivin, serum ACE and ferritin.Median sMR in untreated GD patients was 303.0 ng/mL compared to post-treatment 190.9 ng/mL (p = .02) and healthy controls 202 ng/mL. Median sMR correlated with median spleen volume 455 mL (r = .70, p = .04), liver volume 2025 mL (r = .64, p = .04), BMB 7 (r = .8, p = .03), IgA 1.9 g/L (r = .54, p = .036), IgG 9.2 g/L (r = .57, p = .027), IgM 1.45 g/L (r = .86, p < .0001), with inverse correlation to median platelet count of 125 × 109/L (r = -.47, p = .08) and haemoglobin of 137 g/L (r = -.77, p = .0008). sMR correlated with established biomarkers: osteoactivin 107.8 ng/mL (r = .58, p = .0006), chitotriosidase 3042 nmol/mL/h (r = .52, p = .0006), PARC 800 ng/mL (r = .67, p = .0068), ferritin 547 μg/L (r = .72, p = .002) and CCL3 50 pg/mL (r = .67, p = .007).sMR correlates with clinical features and biomarkers of GD and reduces following therapy.© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
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