[Expression of fibroblast growth factor receptor-4 in fetal kidneys and pathological kidneys of children].
OBJECTIVE
To investigate the expression of fibroblast growth factor receptor-4 (FGFR4) in fetal kidneys and pathological kidneys of children in order to show the roles of fibroblast growth factor (FGF) and FGFR4 in the development of fetal kidneys and renal diseases.


METHODS
The expression of FGFR4 was detected by immumohistochemistry in the normal fetal kidney at 8 to 34 weeks of gestation age (n=18) and 82 children with renal disease, including 28 cases of primary nephrotic syndrome (PNS), 12 acute glomerulonephritis (AGN), 20 Henoch-Schoenlein purpura nephritis (HSPN), and 22 isolated hematuria (IHU). A correlation analysis between renal pathological scores and FGFR4 expression was performed.


RESULTS
1) FGFR4 expression was weakly in renal vesicle and primitive tubules of S-shaped body, irrecognizable in urteric bud and podocytes of C-stage, and negative in mesenchyme and condensing mesenchyme. The immunostaining of FGFR4 was intense in distal tubules and collecting ducts, but was negative in mature glomeruli and proximal tubules. 2) FGFR4 was expressed in all pathological sections of various renal diseases. FGFR4 expression was intense in tubules but weak in glomeruli. It was principally expressed in distal tubules and partially in proximal tubules. The tubules with very strong expressions of FGFR4 presented abnormal structures including dilation and atrophy, especially in proximal tubules. 3) There were no significant differences in the FGFR4 expression in various parts of the kidney among various renal diseases. There were also no significant differences in the FGFR4 expression in renal tubules among the four different pathological types of renal diseases: focal segmental glomerularsclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MsPGN), and minimal change disease (MCD). The FGFR4 expression in podocytes in the MPGN group was noticeably higher than that of the other pathological type group (P < 0.05). 4) The FGFR4 expression in proximal tubules positively correlated with the pathological score of tubules (r=0.463682, P < 0.05) but negatively correlated with the pathological score of glomeruli (r=- 0.0277, P < 0.05). The FGFR4 expression in both distal tubules and podocytes negatively correlated with the pathological score of tubules or glomeruli (P < 0.05).


CONCLUSIONS
The development of fetal kidneys in the early period could not be regulated by FGF-FGFR4 signal which takes part in the development of renal tubules and collecting duct in the mature period. The FGFR4 expression is related with renal pathology in children with PNS, AGN, HSPN or IHU. A proper increase of FGFR4 expression is beneficial to the recovery of renal tissues but an over-expression relates to a severe renal damage.
Zhu
Cui-Ping
CP
Laboratory of Pediatric Nephrology, Second Xiangya Hospital, Central South University, Changsha, China.
Yi
Zhu-Wen
ZW
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005333:Fetus / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry*; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000032:analysis*
C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4