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 inv olved. 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-be ta, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and -negative patients. The a bility 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 ch ange disease were negative for the three TGF-beta isoforms and Tat. In HIVA N, levels of TGF-beta isoforms and Tat were significantly increased, along with the expression of TGF-beta mRNA and deposition of matrix proteins stim ulated by TGF-beta. Increased levels of TGF-beta isoforms, but not Tat, wer e also found in other glomerular diseases characterized by matrix accumulat ion. HN infection, in the absence of HIVAN, was not associated with an incr ease in TGF-beta or Tat expression. Tat stimulated the expression and produ ction of TGF-beta 1 and matrix proteins by human mesangial cells. Conclusions. Our findings suggest that overproduction of TGF-beta is involv ed in the pathogenesis of HIVAN.