Keratinocyte growth factor causes proliferation of urothelium in vivo.
OBJECTIVE
To determine the effect of keratinocyte growth factor (KGF), a mesenchymally derived epithelial growth factor that can cause proliferation of pulmonary, gastrointestinal and mammary epithelia, on urothelium.


METHODS
Recombinant human KGF was systemically administered to rats and Rhesus monkeys, and the proliferative effects on the bladder were evaluated.


RESULTS
Keratinocyte growth factor causes proliferation of transitional epithelial cells. Proliferating cell nuclear antigen (PCNA) expression in rat bladder is dramatically increased along the basal layer of urothelium 1, 3, 7 and 14 days after daily injections of KGF. Incorporation of 5-bromodeoxyuridine (BrdU) at 7 and 14 days in the urothelium of KGF-treated rats parallels PCNA immunoreactivity and confirms that KGF increases DNA synthesis in urothelial cells. Urothelial cell proliferation is accompanied histologically by an increase in mitotic activity. Keratinocyte growth factor-induced PCNA expression is reversible upon cessation of KGF administration. Keratinocyte growth factor mRNA and receptor mRNA are detected by whole organ RNAase protection assays of the urinary bladder and the kidney of normal rats. Rhesus monkeys receiving KGF for 7 days demonstrate a dramatic incorporation of BrdU in the urothelium of the bladder and renal pelvis as well as in the collecting ducts of the kidney.


CONCLUSIONS
Systemic administration of KGF causes rapid and striking proliferation of urothelium.
Yi
E S
ES
Department of Pathology, University of California, San Diego School of Medicine, USA.
Shabaik
A S
AS
Lacey
D L
DL
Bedoya
A A
AA
Yin
S
S
Housley
R M
RM
Danilenko
D M
DM
Benson
W
W
Cohen
A M
AM
Pierce
G F
GF
D000818:Animals; D002455:Cell Division; D004847:Epithelial Cells; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000166:cytology*; D008253:Macaca mulatta; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor / Q000235:genetics; D001743:Urinary Bladder / Q000166:cytology*
C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors