Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases.
Polycystin-2 represents one of so far two proteins found to be mutated in patients with autosomal-dominant polycystic kidney disease. Evidence obtained from experiments carried out in cell lines and with native kidney tissue strongly suggests that polycystin-2 is located in the endoplasmic reticulum. In the kidney, polycystin-2 is highly expressed in cells of the distal and connecting tubules, where it is located in the basal compartment. It is not known whether the expression of polycystin-2 in the kidney changes or whether it can be manipulated under certain instances. Therefore, the distribution of polycystin-2 under conditions leading to acute and chronic renal failure was analyzed. During ischemic acute renal failure, which affects primarily the S3 segment of the proximal tubule, a pronounced upregulation of polycystin-2 and a predominantly combined homogeneous and punctate cytoplasmic distribution in damaged cells was observed. After thallium-induced acute injury to thick ascending limb cells, polycystin-2 staining assumed a chicken wire-like pattern in damaged cells. In the (cy/+) rat, a model for autosomal-dominant polycystic kidney disease in which cysts originate predominantly from the proximal tubule, polycystin-2 immunoreactivity was lost in some distal tubules. In kidneys from (pcy/pcy) mice, a model for autosomal-recessive polycystic kidney disease in which cyst formation primarily affects distal tubules and collecting ducts, a minor portion of cyst-lining cells cease to express polycystin-2, whereas in the remaining cells, polycystin-2 is retained in their basal compartment. Data show that the expression and cellular distribution of polycystin-2 in different kinds of renal injuries depends on the type of damage and on the nephron-specific response to the injury. After ischemia, polycystin-2 may be upregulated by the injured cells to protect themselves. It is unlikely that polycystin-2 plays a role in cyst formation in the (cy/+) rat and in the (pcy/pcy) mouse.
Obermüller
Nicholas
N
Medical Research Center, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany.
Cai
Yiqiang
Y
Kränzlin
Bettina
B
Thomson
R Brent
RB
Gretz
Norbert
N
Kriz
Wilhelm
W
Somlo
Stefan
S
Witzgall
Ralph
R
D000208:Acute Disease; D058186:Acute Kidney Injury / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism; D017044:Polycystic Kidney, Autosomal Recessive / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D050396:TRPP Cation Channels; D013793:Thallium; D014018:Tissue Distribution
D008565:Membrane Proteins; D050396:TRPP Cation Channels; D013793:Thallium