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.