Time course of cytokine mRNA expression in kidneys of rats with unilateralureteral obstruction

The development of renal interstitial fibrosis (RIF) is related to the expr ession and excretion of cytokines and growth factors. Thus, we investigated the time course of mRNA expression of cytokines known as causative factors in a model of RIF in rats before and on day 10 after unilateral ureteral o bstruction (UUO), when first signs of fibrosis were visible, as well as dur ing progressive RIF. UUO causes a fivefold increase in mRNA expression of m onocyte chemoattractant protein 1 15 days after surgery as compared with co ntralateral kidneys. The level remains elevated about three-fold up to day 25. The mRNA of the fibrogenic cytokine transforming growth factor beta 1 ( TGF-beta 1) is increased two- to threefold during the time course, whereas the mRNAs of platelet-derived growth factor B chain (PDGF-B) and its recept or beta (PDGF-RP) increase after UUO, reaching their maxima on days 10-15. PDGF-B mRNA increase up to day 15, marking the onset of fibrosis, and decre ases thereafter, whereas the expression of the PDGF-R beta mRNA remains ele vated more than threefold over the entire study period. Incubation of cultu red renal fibroblasts with TGF-beta 1 and/or PDGF-B suggests that their spe cific action on cell growth and proliferation is maintained even when they are used in combination. The sustained elevation of TGF-beta 1 and PDGF-bet a/PDGF-R beta mRNA levels confirms the assumption of a particular involveme nt of these cytokines in the pathogenesis of RIF. The mRNA expression of th e gap junctional protein connexin 43 in ureteral ligated kidneys is increas ed sixfold already 5 days after UUO. In this way, the increased connexin 43 mRNA levels indicate a possible function in the remodeling of the kidney t issue after tubular damage and fibrosis. Copyright (C) 2000 S. Karger AG, B asel.