Expression and localization of the water channels in human autosomal dominant polycystic kidney disease.
To characterize the cyst-lining cells in human autosomal dominant polycystic kidney disease (ADPKD), we performed immunohistological studies with specific antibodies against human aquaporin-2 (AQP-2, the vasopressin-regulated water channel) and aquaporin-3 (AQP-3), which are expressed only in collecting duct cells in the normal kidney. The polycystic kidney samples were obtained from 2 hemodialysis patient at uninephrectomy. Immunohistochemical studies revealed two types of staining of cyst-lining cells. Approximately 30% of all the cysts were simultaneously immunostained by both antibodies. Among these AQP-positive cysts, more than 90% of the cysts were intensely stained, with well-polarized localization of AQP-2 and AQP-3. In fewer than 10% of AQP-positive cysts, by contrast, immunostaining for AQP-2 and AQP-3 was faint and no clearly polarized localization of the channels was observed. We examined the immunostaining in further detail by electron microscopy. Staining specific for AQP-2 was mainly observed in the apical membrane of cyst-lining cells. Moreover, staining specific for AQP-3 was observed in all of the AQP-2-positive cysts. It appeared unlikely that the variations in immunostaining observed under the light microscope had been induced by total disruption of water-channel polarity. The present study suggests that about 30% of the cysts in our cases of ADPKD were derived from the collecting duct cells and that the cyst-lining cells were well differentiated in terms of AQP expression.
Hayashi
M
M
Department of Internal Medicine, Keio University, School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yamaji
Y
Y
Monkawa
T
T
Yoshida
T
T
Tsuganezawa
H
H
Sasamura
H
H
Kitajima
W
W
Sasaki
S
S
Ishibashi
K
K
Maurmo
F
F
Saruta
T
T
D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels / Q000032:analysis*; D007672:Kidney Cortex / Q000737:chemistry* / Q000473:pathology; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000276:immunology; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000473:pathology
C496023:AQP2 protein, human; C496027:AQP3 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D010446:Peptide Fragments; D051400:Aquaporin 3