NERVE GROWTH-FACTOR RECEPTOR EXPRESSION IN FETAL, MATURE, AND DISEASED HUMAN KIDNEYS

BACKGROUND: Nerve growth factor (NGF) has been proposed to be critical to normal renal development in rodents. However, little is known abou t expression of NGF or its receptors in human kidneys, or their potent ial function in development or disease. EXPERIMENTAL DESIGN: A previou sly characterized monoclonal antibody (NGFR 5) was utilized for immuno histochemical localization of the p75 NGF receptor (NGFR) in alcohol-f ixed tissue sections of human fetal kidney (N=27, 54 to 105 days gesta tion), normal mature kidney obtained from nephrectomies for neoplasia (N=7), and renal biopsies (N=54) with various glomerulopathies previou sly characterized for degree of mesangial ct smooth muscle actin (alph a SM) expression. A second monoclonal antibody (NGFR2) was also utiliz ed on fetal and normal kidney. Immunohistochemical localization of alp ha SM and proliferating cell nuclear antigen expression was also perfo rmed. RESULTS: Glomerular expression of NGFR in the fetus is limited t o the mesangium in later stages of glomerulogenesis; at these stages t his expression is similar to that which has been previously reported f or platelet-derived growth factor receptor-beta and alpha SM. There is focal, weak persistence of NGFR in normal adult glomeruli, similar to alpha SM. In renal biopsies, glomerular NGFR expression was upregulat ed in a variety of disease states, which frequently but not invariably correlated with alpha SM expression. Fetal and adult expression of NG FR is also prominent in periarterial connective tissue cells and nerve . Apparent a e novo expression by many interstitial cells in normal an d diseased adult kidneys is also present. CONCLUSIONS: These studies i ndicate: (a) NGF or other neurotrophins that bind NGFR may be importan t in human kidney development and glomerular response to injury; (b) N GFR is a marker of developing mesangial cells similar to alpha SM and platelet-derived growth factor receptor-beta; (c) enhanced expression of NGFR, like alpha SM, is a marker of mesangial cell injury or activa tion, and that their coordinate upregulation in some glomerular diseas e states appears to recapitulate a normal developmental state; (d) a p opulation of NGFR and platelet-derived growth factor-beta expressing i nterstitial cells can be identified in normal kidneys, which suggests potential signaling mechanisms to recruit or activate these cells at s ites of tubulointerstitial injury.