%0 Journal Article
%T Stabilization of hypoxia inducible factor by cobalt chloride can alter renal epithelial transport
%A Andrew Resnick
%A Subhra Nag
%J Archive of "Physiological Reports".
%D 2017
%R 10.14814/phy2.13531
%X Given the importance of the transcriptional regulator hypoxia©\inducible factor©\1 (HIF©\1) for adaptive hypoxia responses, we examined the effect of stabilized HIF©\1¦Á on renal epithelial permeability and directed sodium transport. This study was motivated by histological analysis of cystic kidneys showing increased expression levels of HIF©\1¦Á and HIF©\2¦Á. We hypothesize that compression induced localized ischemia©\hypoxia of normal epithelia near a cyst leads to local stabilization of HIF©\1¦Á, leading to altered transepithelial transport that encourages cyst expansion. We found that stabilized HIF©\1¦Á 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 ¦Ìmol/L Cobalt chloride (CoCl2) was used acutely to stabilize HIF©\1¦Á in confluent cultures of mouse renal epithelia. We measured increased transepithelial permeability and decreased transepithelial resistance (TER) when HIF©\1¦Á 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
%K Cyst
%K electrophysiology
%K hypoxia
%K ischemia
%K kidney epithelia
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742700/