In vitro investigation of renal epithelial injury suggests that primary cilium length is regulated by hypoxia-inducible mechanisms.
Primary cilia are non-motile sensory organelles that project from cells in many tissues. The role of renal primary cilium-based signalling in regulating epithelial cell proliferation and differentiation is highlighted by studies showing that defects of the cilium lead to epithelial de-differentiation, over proliferation and polycystic kidney disease. Recent studies show that renal primary cilia may also play a role in controlling epithelial differentiation during renal repair. After injury, renal cilium length increases dramatically and then undergoes a normalization that coincides with structural and functional repair in both human patients and mouse models of renal injury. These changes in cilium length are likely to modulate cilium-based signalling, but the injury-related factors that influence renal primary cilium length have yet to be determined. Here, we investigated the effect of three factors commonly associated with renal injury on renal cilium length in an in vitro setting. MDCK (Madin Darby canine kidney) cell cultures bearing primary cilia were treated with BSA to simulate albuminuria, cobalt chloride to simulate hypoxia and the inflammation-related cytokine tumour necrosis factor α. Primary cilium length was only increased in cultures treated with cobalt chloride. Our results suggest a role for hypoxia and the induction of HIF-1α (hypoxia-inducible factor 1α) in increasing renal primary cilium length following renal injury.
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Victoria, Australia.
Elizabeth
E
Verghese
Junli
J
Zhuang
Deshira
D
Saiti
Sharon D
SD
Ricardo
James A
JA
Deane
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D004285:Dogs; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure
D051795:Hypoxia-Inducible Factor 1, alpha Subunit