Nerve growth factor and its monocyte receptors are affected in kidney disease

Nerve growth factor (NGF) plays a critical role in both physiological and pathological conditions. Their biological effects are mediated by two receptors (NGF-R): TrkA and p75. We previously reported NGF and NGF-R overexpression in various renal disorders. The aim of the study was to determinate NGF levels and NGF-R expression in peripheral blood mononuclear cells from subjects affected by glomerulonephritis (GN) and by end-stage renal disease before and after hemodialysis (HD). We enrolled 48 patients with biopsy-proven diagnosis of GN and 16 patients undergoing chronic HD. 25 subjects were enrolled as controls (C). Quantification of NGF in the serum samples was performed using NGF immunoassay. We demonstrated, for the first time, an increased NGF concentration in GN and HD patients compared to C. HD is able to restore serum NGF concentration. In GN, TrkA is overexpressed, whereas p75 did not show any difference versus C. By contrast in HD, TrkA expression is associated with increased p75 levels. In conclusion, NGF can act as protective factor against cytotoxic injuries. p75 plays a role in both survival and death of cells, depending on absence of ligand, cytoplasmic/ligand interaction and interaction with TrkA. The present findings suggest that cell survival during cellular damage is dependent on co-expression of TrkA and p75 and independent of NGF concentration. Further studies are required to confirm these observations.