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Am J Physiol Renal Physiol (January 2, 2002). doi:10.1152/ajprenal.00215.2001
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Articles in PresS, published online ahead of print January 2, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00215.2001
Submitted on July 9, 2001
Accepted on December 28, 2001

Estrogen-Induced Proliferation of Urothelial Cells is Modulated by Nerve Growth Factor

Jian Teng1, Zun-Yi Wang1, and Dale E Bjorling2*

1 Department of Surgical Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, WI, none
2 Department of Surgical Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, WI, none; Department of Surgery, University of Wisconsin-Madison, School of Medicine, Madison, WI, none

* To whom correspondence should be addressed. E-mail: bjorlind{at}svm.vetmed.wisc.edu.

Nerve growth factor (NGF) is a potent inducer of cell proliferation through autophosphorylation of its high-affinity receptor (trkA). Estrogen also modulates proliferation of cells expressing estrogen receptors (ER). Our previous work showed that urothelial cells express both ER{alpha} and ERß, and that trkA, NGF, ER{alpha} and ERß coexist within bladder mucosa. In this report, we examined interaction between estrogen and NGF relative to cell proliferation using primary cultures of human urothelial cells (HUC). 17ß-estradiol (E2, 50 nM), an ER{alpha} agonist (16{alpha}-iodo-17ß-estradiol, 16IE2, 10 nM) and an ERß agonist (genistein, 50 nM ) all stimulated HUC proliferation. These effects were abolished by the estrogen antagonist ICI 182, 780 (100nM). NGF (1-100 ng/ml) also stimulated HUC proliferation, and this effect was abolished by NGF-antiserum (0.1µl/ml) or a trkA antagonist (K252a, 100 nM). HUC proliferation stimulated by E2 was also abolished by NGF-antiserum or K252a. Furthermore, we found E2 stimulated NGF synthesis in HUC, and this effect was inhibited by ICI 182, 780. Immunocytochemical staining and immunoblotting confirmed the expression of ER{alpha}, ERß, and NGF receptors in HUC. Finally, we observed that treatment of HUC with NGF (50 ng/ml) or E2 (50 nM) stimulated trkA phosphorylation, and this effect was abolished by K252a (100 nM) or NGF-antiserum (0.1µl/ml). Taking together, our data indicate that the effects of ER activation on HUC proliferation at least partly involve modulation by NGF via its high-affinity receptor, trkA.




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