Upregulation of monocyte/macrophage HGFIN (Gpnmb/Osteoactivin) expression in end-stage renal disease - PubMed (original) (raw)

Upregulation of monocyte/macrophage HGFIN (Gpnmb/Osteoactivin) expression in end-stage renal disease

Madeleine V Pahl et al. Clin J Am Soc Nephrol. 2010 Jan.

Abstract

Background and objectives: Hematopoietic growth factor-inducible neurokinin 1 (HGFIN), also known as Gpnmb and osteoactivin, is a transmembrane glycoprotein that is expressed in numerous cells, including osteoclasts, macrophages, and dendritic cells. It serves as an osteoblast differentiation factor, participates in bone mineralization, and functions as a negative regulator of inflammation in macrophages. Although measurable at low levels in monocytes, monocyte-to-macrophage transformation causes substantial increase in HGFIN expression. HGFIN is involved in systemic inflammation, bone demineralization, and soft tissue vascular calcification.

Design, setting, participants, & measurements: We explored HGFIN expression in monocytes and monocyte-derived macrophages in 21 stable hemodialysis patients and 22 control subjects.

Results: Dialysis patients exhibited marked upregulation of colony-stimulating factor and IL-6 and significant downregulation of IL-10 in intact monocytes and transformed macrophages. HGFIN expression in intact monocytes was negligible in control subjects but conspicuously elevated (8.6-fold) in dialysis patients. As expected, in vitro monocyte-to-macrophage transformation resulted in marked upregulation of HGFIN in cells obtained from both groups but much more so in dialysis patients (17.5-fold higher). Upregulation of HGFIN and inflammatory cytokines in the uremic monocyte-derived macrophages occurred when grown in the presence of either normal or uremic serum, suggesting the enduring effect of the in vivo uremic milieu on monocyte/macrophage phenotype and function.

Conclusions: Uremic macrophages exhibit increased HGFIN gene and protein expression and heightened expression of proinflammatory and a suppressed expression of anti-inflammatory cytokines. Further studies are needed to determine the role of heightened monocyte/macrophage HGFIN expression in the pathogenesis of ESRD-induced inflammation and vascular and soft tissue calcification.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

Microscopic examination of normal monocytes after overnight culture (A) and after 7 d of culture using normal serum (B) and uremic serum (C).

Figure 2.

Figure 2.

mRNA expression of proinflammatory cytokines (IL-6, TNF), anti-inflammatory cytokines (IL-10), and CSF (a marker/mediator of macrophage transformation) in monocytes from normal control subjects (CTL; A) and patients with ESRD (B) after overnight culture (day 1) and after macrophage transformation (day 7) grown in either control (CS) or uremic serum (US). mRNA levels are presented as a ratio of corresponding values found in the control cells at both day 1 and day 7. *P < 0.05.

Figure 3.

Figure 3.

Comparison of HGFIN mRNA expression in monocytes obtained from control subjects (CTL) and patients with ESRD after overnight culture (day 1; A) and macrophage-transformation (day 7; B). Comparison of HGFIN mRNA levels in ESRD (C) and CTL cells (D) at day 1 and at day 7 after monocyte-macrophage transformation. *P < 0.05.

Figure 4.

Figure 4.

mRNA expression of HGFIN in monocyte-derived macrophages from normal control subjects (CTL) and patients with ESRD grown in either control (CS) or uremic serum (US). mRNA levels are presented as a ratio of the corresponding values found in the control cells at both day 1 and day 7. *P < 0.05.

Figure 5.

Figure 5.

HGFIN protein expression in control and ESRD cells. After overnight incubation (day 1) and macrophage transformation (day 7), cells were grown in normal serum (CS) and uremic serum (US). (A) Representative Western Blot. (B) Group data. (C) Immunocytochemical images of HGFIN protein expression in control and ESRD cells after overnight incubation (day 1) and macrophage transformation (day 7).

Similar articles

Cited by

References

    1. Safadi F, Xu J, Smock S, Rico M, Owen T, Popoff S: Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts. J Cell Biochem 84: 12–26, 2001 - PubMed
    1. Haralanova-Ilieva B, Ramadori G, Armbrust T: Expression of osteoactivin in rat and human liver and isolated rat liver cells. J Hepatol 42: 565–572, 2005 - PubMed
    1. Shikano S, Bonkobara M, Zukas PK, Ariizumi K: Molecular cloning of dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparin sulfate. J Biol Chem 271: 8125–8134, 2001 - PubMed
    1. Bandari PS, Qian J, Yehia G, Joshi D, Maloof PB, Potian J, Oh H, Gascon P, Harrison J, Rameshwar P: Hematopoietic growth factor inducible neurokinin-1 (HGFIN) gene: A transmembrane protein that is similar to neurokinin-1 interacts with substance. Regul Pept 111: 169–178, 2003 - PubMed
    1. Bachner D, Schroder D, Gross G: mRNA expression of the murine glycoprotein (transmembrane) nmb (Gpnmb) gene is linked to the developing retinal pigment epithelium and iris. Brain Res Gene Expr Patterns 1: 159–165, 2002 - PubMed

MeSH terms

Substances

LinkOut - more resources