Transforming growth factor-beta receptor types I and II are expressed in renal tubules and are increased after chronic unilateral ureteral obstruction.
Transforming growth factor-beta (TGF-beta) is a profibrotic cytokine which has been implicated in the renal fibrosis which follows unilateral ureteral obstruction (UUO) in the rat. TGF-beta receptor type I (TGF-RI) and TGF-beta receptor type II (TGF-RII) are part of the complex which mediates the response to TGF-beta. We sought to determine if TGF-RI and TGF-RII are found in the kidney, and if their expression is changed as a result of UUO. Polymerase chain reaction (PCR) was used to determine expression of mRNA for TGF-RI and TGF-RII in the kidney. Immunoperoxidase was used to localize and quantify the expression of these receptors at 3, 7, 14, 21 and 28 days after UUO, and in sham-operated animals. Expression of mRNA for TGF-RI and TGF-RII was demonstrated in sham operated, obstructed and contralateral unobstructed kidneys using PCR. Using immunoperoxidase, a uniform distribution of TGF-RI and TGF-RII was found in cortical tubules of sham operated kidneys, whereas medullary tubules showed a patchy TGF-RI distribution and no TGF-RII staining. After UUO, an increased tubular expression of TGF-RI and TGF-RII was noted in both obstructed and contralateral kidneys compared to sham operated kidneys. No staining for either TGF-RI or TGF-RII was noted in glomeruli, vasculature or interstitial cells. TGF-beta receptors I and II were found exclusively in renal tubules and were shown to increase in both the obstructed and contralateral kidneys relative to sham operated animals. Upregulation of TGF-beta receptors in both kidneys suggests that TGF-beta may contribute to the fibrotic response in the obstructed kidney and the hypertrophic response of the contralateral kidney.
Sutaria
P M
PM
James Buchanan Brady, Department of Urology, Cornell University Medical College, New York, NY 10021, USA.
Ohebshalom
M
M
McCaffrey
T A
TA
Vaughan
E D
ED
Felsen
D
D
D000199:Actins / Q000235:genetics; D000818:Animals; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D007672:Kidney Cortex / Q000737:chemistry; D007679:Kidney Medulla / Q000737:chemistry; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000378:metabolism*
D000199:Actins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta