The mTOR Pathway Is Activated in Human Autosomal-Recessive Polycystic Kidney Disease

Background: An inappropriate activation of the mTOR pathway was demonstrated in the autosomal dominant (AD) form of polycystic kidney disease (PKD). To date it is unclear whether the mTOR pathway is activated in autosomal-recessive (AR) PKD, a cystic disease which occurs in childhood. The purpose of the present study was to evaluate the mTOR pathway in AR PKD. Methods: We evaluated the expression of mTOR pathway molecules in paraffin-embedded liver and kidney samples from patients with AR PKD and control specimens from animals as well as humans. Monoclonal antibodies, the phosphorylated proteins pmTOR, pS6-ribosomal-protein (pS6K), p4E-BP1, peIF4G, and phospho-tuberin/TSC2 were used. Results: mTOR was strongly expressed in renal cyst-lining cells and bile ducts from AR PKD specimen. S6K immunostaining was strong in smaller tubules and weak both in larger renal cysts and in the bile duct epithelium. In controls, mTOR and S6K were expressed in distal tubule segments. 4E-BP1-immunostaining was restricted to noncystic tubules in AR PKD. eIFG4-immunostaining was observed in bile duct epithelium in AR PKD, but not in control tissue. Tuberin/TSC2 immunostaining was negative in all specimens. Conclusion: Our data suggest that the mTOR pathway may be activated in AR PKD, and mTOR molecules may represent a potential target to slow down cyst development in this disease.

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