Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease

Pahl, Madeleine V.; Vaziri, Nosratola D.; Yuan, Jun; Adler, Sharon G.

doi:10.2215/cjn.03390509

Cited by 46 publications

(24 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another gene highly expressed in the interstitium is GPNMB (osteoactivin) that is upregulated during macrophage differentiation from monocytes and appears to function as a negative regulator of inflammation (61). Upregulation of osteoactivin has been observed in monocytes obtained from uremic patients or in normal monocytes cultured in uremic serum (61) as well as in CD11b+ cells within inflammatory myocardial infiltrates in a model of adverse myocardial remodeling (62). In addition this compartment was characterized by a striking NFκB transcriptional profile that was absent in the glomerular “macrophage” signature.…”

Section: Discussionmentioning

confidence: 99%

Cross-Species Transcriptional Network Analysis Defines Shared Inflammatory Responses in Murine and Human Lupus Nephritis

Berthier

Bethunaickan

Gonzalez‐Rivera

et al. 2012

The Journal of Immunology

196

214

View full text Add to dashboard Cite

Lupus nephritis (LN) is a serious manifestation of SLE. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these pre-clinical models. In this study we used an unbiased transcriptional network approach to define in molecular terms similarities and differences between three lupus models and human LN. Genome wide gene expression networks were generated using natural language processing and automated promoter analysis and compared across species via suboptimal graph matching. The three murine models and human LN share both common and unique features. The 20 commonly shared network nodes reflect the key pathologic processes of immune cell infiltration/activation, endothelial cell activation/injury and tissue remodeling/fibrosis, with macrophage/dendritic cell activation as a dominant cross-species shared transcriptional pathway. The unique nodes reflect differences in numbers and types of infiltrating cells and degree of remodeling between the three mouse strains. To define mononuclear phagocyte derived pathways in human LN, gene sets activated in isolated NZB/W renal mononuclear cells were compared with human LN kidney profiles. A tissue compartment specific macrophage activation pattern was seen, with NFκB1 and PPARγ as major regulatory nodes in the tubulointerstitial and glomerular networks respectively. Our study defines which pathologic processes in murine models of LN recapitulate the key transcriptional processes active in human LN and suggests that there are functional differences between mononuclear phagocytes infiltrating different renal microenvironments.

show abstract

Section: Discussionmentioning

confidence: 99%

Cross-Species Transcriptional Network Analysis Defines Shared Inflammatory Responses in Murine and Human Lupus Nephritis

Berthier

Bethunaickan

Gonzalez‐Rivera

et al. 2012

The Journal of Immunology

196

214

View full text Add to dashboard Cite

show abstract

“…These findings allow the hypothesis that OA could be involved in the pathophysiological cascade of tissue injury and repair. In addition, uremic Mf in patients with end-stage renal disease have been recently demonstrated to exhibit increased levels of this protein (68). OA was found overexpressed in various malignant tumors (65,69,70); moreover, it has been described that overexpression of OA in glioma and hepatoma cell lines sustains tumor invasiveness (65,71).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

Solinas

Schiarea

Liguori

et al. 2010

The Journal of Immunology

348

292

View full text Add to dashboard Cite

Tumor-associated macrophages (TAMs) are key orchestrators of the tumor microenvironment directly affecting neoplastic cell growth, neoangiogenesis, and extracellular matrix remodeling. In turn, the tumor milieu strongly influences maturation of TAMs and shapes several of their features. To address the early macrophage (Mϕ) differentiation phase in a malignant context, we mimicked a tumor microenvironment by in vitro coculturing human blood monocytes with conditioned media from different cancer cell lines. Only 2 out of 16 tumor cell lines induced Mϕ differentiation due to secreted M-CSF isoforms, including high molecular mass species. A global gene profiling of tumor-conditioned Mϕ was performed. Comparison with other datasets (polarized M1-Mϕ, M2-Mϕ, and TAMs isolated from human tumors) highlighted the upregulation of several genes also shared by TAM and M2-polarized Mϕ. The most expressed genes were selenoprotein 1, osteoactivin, osteopontin, and, interestingly, migration-stimulating factor (MSF), a poorly studied oncofoetal isoform of fibronectin. MSF (present in fetal/cancer epithelial and stromal cells but not in healthy tissues) was never identified in Mϕ. MSF production was confirmed by immunohistochemistry in human TAMs. MSF was induced by M-CSF, IL-4, and TGFβ but not by proinflammatory stimuli. RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization of Mϕ. Tumor-conditioned Mϕ-derived MSFs strongly stimulated tumor cell migration, thus contributing to the motile phenotype of neoplastic cells. In conclusion, MSF is a new molecule associated with the M2 polarization of Mϕ and expressed by TAMs. Its biological function may contribute to Mϕ-mediated promotion of cancer cell invasion and metastasis.

show abstract

“…These abnormalities point to spontaneous activation of monocytes and their contribution to the prevailing oxidative stress and systemic inflammation in ESRD. In addition the uremic plasma induces production of osteoactivin by monocytes and macrophages which can contribute to the prevailing vascular calcification in the ESRD population (27). Likewise uremic plasma stimulates adhesion and infiltration of normal monocytes in cultured human endothelial monolayer used to simulate arterial wall in vitro (28) pointing to the pro-atherogenic properties of uremic milieu.…”

Section: Effects Of Ckd On Components Of Innate Immunitymentioning

confidence: 99%

Effect of Uremia on Structure and Function of Immune System

Vaziri¹,

Pahl²,

Crum³

et al. 2012

Journal of Renal Nutrition

Self Cite

294

239

View full text Add to dashboard Cite

End stage renal disease (ESRD) is simultaneously associated with immune activation, marked by systemic inflammation, and immune deficiency. Systemic inflammation contributes to atherosclerosis, cardiovascular disease, cachexia and anemia, while immune deficiency leads to impaired response to vaccination, and increased incidence and severity of microbial infections. ESRD-associated inflammation and immune deficiency are associated with: a) General expansion of monocytes and elevations of their basal integrin, Toll-like receptor (TLR)-2, and TLR-4 expression, cytokine production, and reactive oxygen species (ROS) generation and reduced phagocytic capacity, b) Depletion and impaired inhibitory activity of regulatory T cells (Treg), c) Spontaneous activation, degranulation, increased basal ROS production, decreased phagocytic capacity and increased apoptosis of the circulating polymorphonuclear leukocytes (PMNs), d) Upregulation of ROS production machinery and chemokine expression in the cellular constituents of various tissues, highlighting participation of non-immune cells in the prevailing inflammatory state. e) Depletion of the antigen-presenting dendritic cells (DC), f) Reduced CD4/CD8 T cell ratio and depletion of naïve and central memory T cells, g) Diffuse B cell lymphopenia leading to impaired humoral immunity, and h) Increased pro-inflammatory activity of LDL and reduced anti-inflammatory capacity of HDL. Thus, ESRD-associated inflammation is due to activation of innate immune system, orchestrated by monocytes, macrophages, granulocytes and cellular constituents of other organs/tissues. This is coupled with immune deficiency which is caused by depletion of dendritic cell, naïve and central memory T cells and B cells and impaired phagocytic function of PMNs and monocytes.

show abstract

Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease

Cited by 46 publications

References 33 publications

Cross-Species Transcriptional Network Analysis Defines Shared Inflammatory Responses in Murine and Human Lupus Nephritis

Cross-Species Transcriptional Network Analysis Defines Shared Inflammatory Responses in Murine and Human Lupus Nephritis

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

Effect of Uremia on Structure and Function of Immune System

Contact Info

Product

Resources

About