Increased levels of transforming growth factor-beta in HIV-associated nephropathy.
BACKGROUND
Human immunodeficiency virus-associated nephropathy (HIVAN) is a renal disease of unknown pathogenesis. Recent evidence suggests that the fibrogenic cytokine transforming growth factor-beta (TGF-beta) might be involved. We hypothesized that overproduction of TGF-beta in the kidney might be involved in the pathogenesis of HIVAN.


METHODS
The mRNA and protein expression of TGF-beta isoforms, TGF-beta 1, TGF-beta 2, and TGF beta 3, deposition of matrix proteins induced by TGF-beta, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and -negative patients. The ability of Tat to induce production of TGF-beta and matrix proteins was also studied in human mesangial cells.


RESULTS
Normal kidneys, thin basement membrane nephropathy, and minimal change disease were negative for the three TGF-beta isoforms and Tat. In HIVAN, levels of TGF-beta isoforms and Tat were significantly increased, along with the expression of TGF-beta mRNA and deposition of matrix proteins stimulated by TGF-beta. Increased levels of TGF-beta isoforms, but not Tat, were also found in other glomerular diseases characterized by matrix accumulation. HIV infection, in the absence of HIVAN, was not associated with an increase in TGF-beta or Tat expression. Tat stimulated the expression and production of TGF-beta 1 and matrix proteins by human mesangial cells.


CONCLUSIONS
Our findings suggest that overproduction of TGF-beta is involved in the pathogenesis of HIVAN.
Yamamoto
T
T
Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, USA.
Noble
N A
NA
Miller
D E
DE
Gold
L I
LI
Hishida
A
A
Nagase
M
M
Cohen
A H
AH
Border
W A
WA
D016263:AIDS-Associated Nephropathy / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus