Altered expression of c-kit-positive cells in the ureterovesical junction after surgically created vesicoureteral reflux.
OBJECTIVE
Peristaltic contractions propel urine unidirectionally from the renal pelvis trough the ureter and into the bladder. A morphologically and functionally competent ureterovesical junction prevents vesicoureteral reflux (VUR). According to current knowledge, pyeloureteral peristalsis is driven by atypical muscle cells within the upper urinary tract. Another likely relevant cell population, which is c-kit-positive, has been shown to be present within the whole urinary tract. Morphological changes of c-kit-positive cells have been described in VUR and pyeloureteral junction (PUJ) obstruction. Nevertheless, the functional importance of c-kit-positive interstitial cells has not yet been elucidated fully. Therefore, we investigated the influence of experimentally created VUR on the expression of c-kit-positive cells.


METHODS
We created left-sided unilateral VUR in eight Vietnamese pigs using an open surgical technique. The VUR was shown to be grade II-III by voiding cystourethrogram (VCUG), 1 and 6 months after the procedure. The animals were killed after 6 months. The vesicoureteral junction and the distal ureters were excised and fixed in 4% PFA. Paraffin sections were stained using c-kit immunohistochemistry. A quantitative evaluation was performed by two independent investigators. The unaffected, contralateral, nonrefluxing ureters served as controls.


RESULTS
We identified two types of c-kit-immunoreactive cells within the ureterovesical junction and distal ureter. The first group was comprised of round-shaped cells with substantial intracellular granulas, which resembled mast cells. Mast cells were found in the subepithelial region as well as between the muscle bundles. The number of mast cells was slightly increased in the VUR group. The second group consisted of spindle-shaped, bipolar ICC-like cells, which were seen mainly in the submucosal and muscular layers. The number of spindle-shaped c-kit-immunoreactive cells was markedly decreased in the refluxing ureter compared to the controls.


CONCLUSIONS
Surgically created VUR leads to altered expression of c-kit-positive cells. The altered distribution of c-kit-positive ICC-like cells might further contribute to the impairment of coordinated pyeloureteral peristalsis.
Oberritter
Zsolt
Z
Department of Paediatric Surgery, University of Pecs, Pecs, Hungary. zsoltoberritter@gmail.com
Rolle
Udo
U
Juhasz
Zsolt
Z
Cserni
Tamas
T
Puri
Prem
P
D000818:Animals; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D014513:Ureter / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014718:Vesico-Ureteral Reflux / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D019009:Proto-Oncogene Proteins c-kit