Department of Medicine, Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Building 53, Room 125, Rt 81, Orange, CA 92868, USA.
Clin J Am Soc Nephrol. 2010 Jan;5(1):56-61. doi: 10.2215/CJN.03390509. Epub 2009 Oct 15.
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.
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.
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.
造血生长因子诱导神经激肽 1（HGFIN），也称为 Gpnmb 和骨激活素，是一种跨膜糖蛋白，在许多细胞中表达，包括破骨细胞、巨噬细胞和树突状细胞。它作为成骨细胞分化因子，参与骨矿化，并作为巨噬细胞炎症的负调节剂。尽管单核细胞中可测到低水平的 HGFIN，但单核细胞向巨噬细胞的转化导致 HGFIN 表达显著增加。HGFIN 参与全身炎症、骨脱矿化和软组织血管钙化。
设计、设置、参与者和测量：我们研究了 21 例稳定血液透析患者和 22 例对照者单核细胞和成单核细胞来源的巨噬细胞中的 HGFIN 表达。
透析患者的完整单核细胞和转化巨噬细胞中集落刺激因子和白细胞介素-6 明显上调，白细胞介素-10 显著下调。对照组完整单核细胞中 HGFIN 表达可忽略不计，但透析患者明显升高（8.6 倍）。正如预期的那样，体外单核细胞向巨噬细胞的转化导致两组细胞中 HGFIN 的显著上调，但在透析患者中上调更为明显（高 17.5 倍）。在正常或尿毒症血清存在的情况下，尿毒症来源的单核细胞衍生的巨噬细胞中 HGFIN 和炎症细胞因子的上调表明体内尿毒症微环境对单核细胞/巨噬细胞表型和功能的持久影响。
尿毒症巨噬细胞表现出 HGFIN 基因和蛋白表达增加，促炎细胞因子表达升高，抗炎细胞因子表达降低。需要进一步研究来确定单核细胞/巨噬细胞 HGFIN 表达增加在 ESRD 诱导的炎症和血管及软组织钙化发病机制中的作用。
