Wnt/β-catenin signalling and podocyte dysfunction in proteinuric kidney disease

Lili Zhou, Youhua Liu
Nature Reviews. Nephrology 2015, 11 (9): 535-45
Podocytes are unique, highly specialized, terminally differentiated cells that are integral components of the kidney glomerular filtration barrier. Podocytes are vulnerable to a variety of injuries and in response they undergo a series of changes ranging from hypertrophy, autophagy, dedifferentiation, mesenchymal transition and detachment to apoptosis, depending on the nature and extent of the insult. Emerging evidence indicates that Wnt/β-catenin signalling has a central role in mediating podocyte dysfunction and proteinuria. Wnts are induced and β-catenin is activated in podocytes in various proteinuric kidney diseases. Genetic or pharmacologic activation of β-catenin is sufficient to impair podocyte integrity and causes proteinuria in healthy mice, whereas podocyte-specific ablation of β-catenin protects against proteinuria after kidney injury. Mechanistically, Wnt/β-catenin controls the expression of several key mediators implicated in podocytopathies, including Snail1, the renin-angiotensin system and matrix metalloproteinase 7. Wnt/β-catenin also negatively regulates Wilms tumour protein, a crucial transcription factor that safeguards podocyte integrity. Targeted inhibition of Wnt/β-catenin signalling preserves podocyte integrity and ameliorates proteinuria in animal models. This Review highlights advances in our understanding of the pathomechanisms of Wnt/β-catenin signalling in mediating podocyte injury, and describes the therapeutic potential of targeting this pathway for the treatment of proteinuric kidney disease.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"