Hepatic ischemia/reperfusion injury disrupts the homeostasis of kidney primary cilia via oxidative stress

Abstract

Acute kidney injury (AKI) is a major complication of hepatic surgeries. The primary cilium protrudes to the lumen of kidney tubules and plays an important role in renal functions. Disruption of primary cilia homeostasis is highly associated with human diseases including AKI. Here, we investigated whether transient hepatic ischemia induces length change and deciliation of kidney primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress regulates those. HIR induced damages to the liver and kidney with increases in ROS/oxidative stress. HIR shortened the cilia of kidney epithelial cells and caused them to shed into the urine. This shortening and shedding of cilia was prevented by Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, an antioxidant). The urine of patient undergone liver resection contained ciliary proteins. These findings indicate that HIR induces shortening and deciliation of kidney primary cilia into the urine via ROS/oxidative stress, suggesting that primary cilia is associated with HIR-induced AKI and that the presence of ciliary proteins in the urine could be a potential indication of kidney injury.

Aldosterone controls primary cilium length and cell size in renal collecting duct principal cells

“…42 Conversely, acute kidney injury which results in decreased GFR and, therefore, Na + delivery to renal tubule epithelial cells causes primary cilium shortening via reactive oxygen species/oxidative stress response mechanism. 37,39 The present study demonstrates that primary cilium length is linked to transepithelial Na + transport, independent of ENaC expression levels. This suggests that the GFR-related changes in primary cilium length relies, at least in part, on alteration of intracellular Na + influx and/or concentration.…”

“…For instance, unilateral nephrectomy, which is associated with increased GFR and tubular Na + delivery, leads to ciliary elongation in epithelial cells of the remnant kidney . Conversely, acute kidney injury which results in decreased GFR and, therefore, Na + delivery to renal tubule epithelial cells causes primary cilium shortening via reactive oxygen species/oxidative stress response mechanism . The present study demonstrates that primary cilium length is linked to transepithelial Na + transport, independent of ENaC expression levels.…”

“…Although ciliary length is defined by the cell type, it is regulated by environmental stimuli and may modulate the functional activity of the organelle . In the kidney, the length of primary cilia is regulated by via an adaptive mechanism in response to changes in glomerular filtration rate (GFR) and, therefore, electrolyte delivery to the ASDN . For instance, unilateral nephrectomy, which is associated with increased GFR and tubular Na + delivery, leads to ciliary elongation in epithelial cells of the remnant kidney .…”

“…4,37,38 In the kidney, the length of primary cilia is regulated by via an adaptive mechanism in response to changes in glomerular filtration rate (GFR) and, therefore, electrolyte delivery to the ASDN. 37,39,40 For instance, unilateral nephrectomy, F I G U R E 6 Aldosterone stabilizes IFT88 by inhibiting its degradation in collecting duct principal cells. Confluent mCCD cl1 cells grown on polycarbonate filters were incubated in serum-and hormone-deprived medium for 24 hours in the absence (0 hours Aldo) or presence of 10 −6 M aldosterone (Aldo) for 3, 6, or 9 hours.…”

Intraflagellar transport-A deficiency attenuates ADPKD in a renal tubular- and maturation-dependent manner

“…In the jck non-orthologous ADPKD mouse model, renal primary cilia are also lengthened, and pharmacological shortening of primary cilia in jck mutant mice was associated with an attenuation of the ADPKD phenotype 19,39 . Moreover, cilia length is altered also in acute kidney injury and chronic kidney disease [40][41][42][43] . Thus, to understand mechanisms of renal tubule homeostasis, the connections between cilia length and cilia function, and renal disease require deeper study.…”