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عنوان فارسی مقاله:
قطعات سیگنالینگ بویایی و گیرنده های بویایی در سلول های توبول کلیه انسان
عنوان انگلیسی مقاله:
Olfactory signaling components and olfactory receptors are expressed in tubule cells of the human kidney
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Olfactory receptors (ORs) are G protein-coupled receptors (GPCRs) that form the largest known gene superfamily in the human genome. Their expression was first described in the olfactory epithelium (OE) [1]. However, current studies have also verified the functional expression of ORs in non-olfactory human tissues, where they play essential roles in physiological processes. For example, ORs impact sperm motility [2], inhibition of proliferation of prostate and liver cancer cells, as well as myelogenous leukemia cells [3e5], wound healing of human skin [6], and serotonin release of enterochromaffin cells [7]. Therefore, ORs seem to have diverse physiological and pathophysiological functions and are interesting targets for basic and clinical research approaches. In olfactory sensory neurons, the binding of an odorant to an OR leads to the activation of a cAMP-mediated signaling pathway. The olfactory specific G protein Gaolf is activated after the conformational change of the receptor and in turn activates adenylyl cyclase III (ACIII), which converts ATP to cAMP [8e10]. The production of cAMP leads to the opening of cyclic nucleotide-gated (CNG) channels and an influx of Ca2þ into the sensory neuron [11,12]. Interestingly, a previous study revealed the expression of olfactory signaling components Gaolf and ACIII in cells of the macula densa of rat and mice kidney [13]. ACIII-deficient mice showed a reduced glomerular filtration rate (GFR), and it is assumed that both Gaolf and ACIII play a role in the regulation of the GFR and blood pressure [14]. Further, OR78, a short chain fatty acid (SCFA)-activated receptor, is expressed in cells of the macula densa and has an impact on the modulation of blood pressure and renin secretion in the mouse kidney. ORs are therefore good candidates for the detection of fatty acids dissolved within the filtrate of the kidney glomeruli. The production of SCFA is associated with the fermentation of gut microbiota, but the accumulation of SCFA can also occur during pathological processes and change the odor of the urine. Patients with isovaleric aciduria, a genetic disorder of the leucine metabolism, exhibit an increased accumulation of isovaleric acid (IVA) that gives urine the odor of sweaty feet [15]. Until now, no studies have documented expression of ORs in cells of the human kidney. In this study, we demonstrated that some components of the olfactory signaling cascade and OR51E1 and OR11H7 are expressed in the human proximal tubule cell line HK-2. We showed that HK-2 cells can be activated by IVA, a ligand for OR51E1 and OR11H7. These findings could be useful for understanding the modulation of renal physiology by SCFA-sensing GPCRs.
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