Role of oxygen and the HIF-pathway in polycystic kidney disease
Buchholz B, Eckardt KU (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 69
Article Number: 109524
DOI: 10.1016/j.cellsig.2020.109524
Abstract
Kidney cyst growth in ADPKD is associated with regional hypoxia, presumably due to a mismatch between enlarged cysts and the peritubular capillary blood supply and compression of peritubular capillaries in cyst walls. Regional hypoxia leads to activation of hypoxia-inducible transcription factors, with the two main HIF isoforms, HIF-1 and HIF-2 expressed in cyst epithelia and pericystic interstitial cells, respectively. While HIF-2 activation is linked to EPO production, mitigating the anemia that normally accompanies chronic kidney disease, HIF-1 promotes cyst growth. HIF-dependent cyst growth is primarily due to an increase in chloride-dependent fluid secretion into the cyst lumen. However, given the broad spectrum of HIF-target genes, additional HIF-mediated pathways may also contribute to cyst progression. Furthermore, hypoxia can influence cyst growth through the generation of reactive oxygen species. Since cyst expansion aggravates regional hypoxia, a feedforward loop is established that accelerates cyst expansion and disease progression. Inhibiting the HIF pathway and/or HIF target genes that are of particular relevance for HIF-dependent cyst fluid secretion may therefore represent novel therapeutic approaches to retard the progression of APDKD.
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Germany (DE)How to cite
APA:
Buchholz, B., & Eckardt, K.-U. (2020). Role of oxygen and the HIF-pathway in polycystic kidney disease. Cellular Signalling, 69. https://doi.org/10.1016/j.cellsig.2020.109524
MLA:
Buchholz, Björn, and Kai-Uwe Eckardt. "Role of oxygen and the HIF-pathway in polycystic kidney disease." Cellular Signalling 69 (2020).
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