Tumor necrosis factor-α inhibits epithelial differentiation and morphogenesis in the mouse metanephric kidney in vitro
International Journal of Developmental Biology, Volume 42, No. 5, Year 1998
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Tumor necrosis factor-α (TNF-α), an inflammatory cytokine, has diverse actions both within and outside the immune system and has been implicated in the etiology of a wide range of pathological conditions. Evidence is accumulating that it may also have important roles in the normal development of the embryo. In this study we demonstrated that the addition of recombinant TNF-α to metanephric organ culture induced a dose dependent and reversible decrease in growth and development, with inhibition of ureteric bud branching and nephron formation beyond the condensate stage and despite appropriate expression of the transcription factor pax-2. TNF-α also increased the point prevalence of apoptosis after only 1 day of culture. We also noted that macrophages were present in renal rudiments at the inception of nephrogenesis and their numbers significantly increased during the culture period. This effect was enhanced by TNF-α. We have also demonstrated expression of mRNAs for TNF-α and its receptors in whole mouse metanephroi from the inception of renal development. TNF-α protein was also detected, predominantly at mesenchymal/epithelial interfaces. In addition, TNF-α mRNA and protein were expressed by clonal renal mesenchymal cells in vitro, suggesting that these cells are a source of TNF-α in vivo.