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Symmetric muscular contractions and unidirectional peristalsis are
prerequisites for a competent valve function at the ureterovesical
junction (UVJ). Interstitial cells of Cajal (ICC¥s) are pacemaker cells
that create and coordinate peristaltic motility. Ureteral endings were
immunohistochemically investigated to elucidate the presence of ckit
positive ICC¥s as well as the occurrence of gap junction protein
connexin 43 (Cx43) in children with vesicoureteral reflux (VUR) to
identify a possible pathogenetic factor of an insufficient anti-reflux
mechanism. Distal ureteral specimens were obtained from 27
children undergoing anti-reflux surgery. Routine histological paraffin
embedded sections were immunostained detecting the c-kit
protooncogene to study the presence of ICC¥s as well as Cx43
positive cells to determine the gap junction density within the ureteral
wall. Age matched nonrefluxing ureteral endings served as controls.
All investigations were done on the basis of high power field
magnification for semiquantitative analysis and statistically analyzed.
ICC¥s were present in both refluxing and nonrefluxing ureteral
endings. Healthy individuals displayed significantly more ICC¥s than
children with VUR. Connexin 43 immunoreactivity was significantly
reduced in all refluxing ureteral specimens, whereas it was
homogenously distributed in normal controls. Refluxing ureteral
endings sigificantly lack these pacemaker cells implying a malfunctioning valve mechanism permitting VUR. A substantial
reduction of gap junctions in this region adversely affects intercellular
signalling aggravating coordinated peristalsis which is essential for a
competent anti-reflux mechanism.