-transparent.png){kind=logo}
BACKGROUND Nerve growth factor (NGF) has been proposed to be critical to normal renal development in rodents. However, little is known about expression of NGF or its receptors in human kidneys, or their potential function in development or disease. METHODS A previously characterized monoclonal antibody (NGFR 5) was utilized for immunohistochemical localization of the p75 NGF receptor (NGFR) in alcohol-fixed tissue sections of human fetal kidney (N = 27, 54 to 105 days gestation), normal mature kidney obtained from nephrectomies for neoplasia (N = 7), and renal biopsies (N = 54) with various glomerulopathies previously characterized for degree of mesangial alpha smooth muscle actin (alpha SM) expression. A second monoclonal antibody (NGFR2) was also utilized on fetal and normal kidney. Immunohistochemical localization of alpha SM and proliferating cell nuclear antigen expression was also performed. RESULTS Glomerular expression of NGFR in the fetus is limited to the mesangium in later stages of glomerulogenesis; at these stages this expression is similar to that which has been previously reported for 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 upregulated in a variety of disease states, which frequently but not invariably correlated with alpha SM expression. Fetal and adult expression of NGFR is also prominent in periarterial connective tissue cells and nerve. Apparent de novo expression by many interstitial cells in normal and diseased adult kidneys is also present. CONCLUSIONS These studies indicate: (a) NGF or other neurotrophins that bind NGFR may be important in human kidney development and glomerular response to injury; (b) NGFR 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 activation, and that their coordinate upregulation in some glomerular disease states appears to recapitulate a normal developmental state; (d) a population of NGFR and platelet-derived growth factor-beta expressing interstitial cells can be identified in normal kidneys, which suggests potential signaling mechanisms to recruit or activate these cells at sites of tubulointerstitial injury.
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
January 2007,
Journal of nephrology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
May 1991,
Molecular and cellular endocrinology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
October 1993,
Nihon Jinzo Gakkai shi,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
April 2007,
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
January 2003,
Gerontology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
February 1988,
Developmental biology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
July 1988,
Annals of neurology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
January 1991,
International review of cytology,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
May 1996,
Nihon Jinzo Gakkai shi,
C E Alpers, and
K L Hudkins, and
M Ferguson, and
R J Johnson, and
G C Schatteman, and
M Bothwell
July 2003,
The Journal of comparative neurology,
