Wnt-signaling pathways in progressive renal fibrosis

The prevention and potential reversal of interstitial fibrosis is a central strategy for the treatment of progressive renal disease. This strategy requires a better understanding of the underlying pathophysiologic processes involved in progressive renal fibrosis.

The developmental processes in which Wnt (combination of 'wingless' and 'INT')/frizzled signaling is involved is discussed in this review, including cell fate determination, cell polarity, tissue patterning and control of cell proliferation. These pathways are also active in the adult where they play key roles in the maintenance of tissue homeostasis, wound repair and chronic tissue damage.

Wnt biology helps to control cell polarity, moderates cell proliferation and underlies other processes linked to renal homeostasis. Reactivation and dysregulation of the Wnt pathways underlie chronic fibrosis and progressive renal failure. Wnt signaling is, however, context-dependent: the pathways are complex and undergo many levels of cross-talk with other regulatory systems and regulatory pathways. On one hand, this may help to explain the positive effects of Wnt-signaling blockades seen in some animal models of chronic renal damage and, on the other, this suggests that it may be difficult to predict how modifications of the Wnt pathway may influence a process.