Figure 10.

Working model linking obstruction, TGF-β1 and PAX2 in human kidneys. Increased hydrostatic pressure from impairment of fetal urinary flow is postulated to trigger cystic epithelial hyperproliferation, mediated via up-regulation of PAX2, and to directly up-regulate TGF-β1. Increased levels of this cytokine act as a biological brake on epithelial hyperproliferation, inhibit normal branching morphogenesis, and promote phenotypic transformation of epithelial cells and their loss into a mesenchyme-like phenotype. The final biological effects therefore represent a balance between these positive and negative factors. Other triggers such as mutations or teratogens may also initiate this sequence of events. → indicates stimulates or causes; indicates inhibits or prevents.