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Constitutive activation of nf-κb causes tubule enlargement and cyst formation in cultured mammalian collecting duct cells

Liping Suna, Chaofeng Hub, Shixuan Wangc, Xinzhou Zhang

Polycystic kidney disease (PKD) is characterized by progressive enlargement of renal cysts. It is widely accepted that cystogenesis is mostly due to the disturbance in the balance between the proliferation and apoptosis of the tubular epithelial cells. We have previously demonstrated an increase in nuclear factor κB (NF-κB) in fibrocystindecreased kidney cells. The aim of the present study was to determine the effect of NF-κB signaling on cyst formation, tubular cell apoptosis and proliferation in the mCCD cells, an in vitro model of tubulogenesis that would be suitable for experimental induction of cyst formation. Selective activation of NF-κB pathway using TNF-α resulted in progressive dilatation of existing tubules, leading to the formation of cyst-like structures. The caspase- 3 inhibitor reduced tubular apoptosis and proliferation and prevented tubule enlargement and cyst formation. We conclude that NF-κB signaling plays a key role in renal cyst formation, at least in part by inhibiting caspase-3 activity. These observations provide a potential platform for the future treatment of the renal manifestations of PKD.