Abstract

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to hypoxia-induced renal injury. Unlike hypoxic adult kidneys, hypoxic fetal kidneys are characterized by interstitial edema, tubular disparition and atrophy. We also noted that there is an increase in the cilia length as well as an increase in the cilia function in the hypoxic fetal proximal and distal collecting epithelia. Hypoxia, however, has no significant effect on primary cilia in the adult kidneys. Increased cilia length is also associated with greater flow-induced intracellular calcium signaling in renal epithelial cells from hypoxic fetuses. Our studies suggest that while hypoxia causes renal fibrosis in both adult and fetal kidneys, hypoxia-induced alteration in cilia length and function are specific to more severe renal injuries in fetal hypoxic kidneys.

Highlights

  • Hypoxic environments in humans can result in the high-altitude renal syndrome (HARS) (Arestegui et al, 2011)

  • Capillary loops of the glomeruli were normal, and the number and morphology of endothelial cells were comparable between normoxic and hypoxic tissues

  • Our studies show that the length of primary cilia in distal collecting tubules become longer during maturation, while there is no change in proximal tubule cilia length from fetuses to adults

Read more

Summary

Introduction

Hypoxic environments in humans can result in the high-altitude renal syndrome (HARS) (Arestegui et al, 2011). The kidneys have a fundamental role in adaption to regulate body fluids, electrolyte and acid-base homeostasis during acclimatization to high altitude and in mountain sickness syndromes. Kidneys respond to hypoxic diuresis and natriuresis through inhibition of renal tubular sodium reabsorption, in addition to erythropoietin production (Haditsch et al, 2015). Kidneys are very susceptible to lowered oxygen tensions (Mayer, 2011; Fu et al, 2016). Kidneys exhibit defense mechanisms centered around the activation of hypoxia-inducible

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call