Stabilization of hypoxia inducible factor by cobalt chloride can alter renal epithelial transport

Given the importance of the transcriptional regulator hypoxia‐inducible factor‐1 (HIF‐1) for adaptive hypoxia responses, we examined the effect of stabilized HIF‐1α on renal epithelial permeability and directed sodium transport. This study was motivated by histological analysis of cystic kidneys showing increased expression levels of HIF‐1α and HIF‐2α. We hypothesize that compression induced localized ischemia‐hypoxia of normal epithelia near a cyst leads to local stabilization of HIF‐1α, leading to altered transepithelial transport that encourages cyst expansion. We found that stabilized HIF‐1α alters both transcellular and paracellular transport through renal epithelial monolayers in a manner consistent with secretory behavior, indicating localized ischemia‐hypoxia may lead to altered salt and water transport through kidney epithelial monolayers. A quantity of 100 μmol/L Cobalt chloride (CoCl(2)) was used acutely to stabilize HIF‐1α in confluent cultures of mouse renal epithelia. We measured increased transepithelial permeability and decreased transepithelial resistance (TER) when HIF‐1α was stabilized. Most interestingly, we measured a change in the direction of sodium current, most likely corresponding to abnormal secretory function, supporting our positive‐feedback hypothesis.