Document Type

Article

Publication Date

12-1-2017

Publication Title

Physiological Reports

Abstract

© 2017 The Authors. 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 (CoCl2) 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.

DOI

10.14814/phy2.13531

Version

Publisher's PDF

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Volume

5

Issue

24

Included in

Physics Commons

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