Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently in Adult and Fetal Ovine Kidneys

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.

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas

“…On the one hand, staying at plateau areas caused liver dysfunction through endoplasmic reticulum stress and subsequent apoptosis, decreased expression content of hepatic microsomal enzyme, and might also be related to the enzyme's activity changes ( 22 , 23 ). On the other hand, exposure to high-altitude exerted significant effects on kidney injury by the alteration of cilia length and function which was resulted from the renal hypoperfusion caused by the chronic hypobaric hypoxic environment ( 24 , 25 ). Taking together, TBI and high-altitude jointly lead to the liver and renal injury through a series of complicated mechanisms, which may provide basics for treatment and should be further explored.…”

HeLa Cervical Cancer Cells Are Maintained by Nephronophthisis 3-Associated Primary Cilium Formation via ROS-Induced ERK and HIF-1α Activation under Serum-Deprived Normoxic Condition

“…Previous reports showed that the effect of hypoxic conditions on PC formation, length and function is a little complicated with cell type and developmental stage. The percent of elongated cilia reduced significantly in rat tail tendon fascicles under hypoxic conditions, but the cilia length and function increased in the hypoxic fetal proximal and distal collecting epithelia [ 62 , 63 ]. It might be due to many other molecular changes as well as HIF-1α under hypoxic conditions.…”

Phosphosite T674A mutation in kinesin family member 3A fails to reproduce tissue and ciliary defects characteristic of CILK1 loss of function

“…[25][26][27] Cilia turnover is intrinsically linked to cell cycle progression and cell growth conditions such as starvation and hypoxia. [28][29][30] Alterations of ciliary dynamics under pathological conditions can influence cell fate choices and tissue homeostasis. 31 Third, we have not determined the impact of Kif3a T674A mutation on organ systems other than lung, skeleton, and brain.…”