Abstract
Current cigarette smoking is associated with chronic kidney disease (CKD) or death from end-stage renal disease (ESRD). Mainstream cigarette smoke includes over 4000 compounds. Among the compounds present in tobacco smoke, nicotine is one of a large number of biologically stable and active compounds present in tobacco. However, the mechanisms by which nicotine exacerbates kidney disease progression have not been identified. It is known that the inflammasomes constitute an important innate immune pathway and contribute to the pathophysiology of diverse kidney diseases. The relationship between inflammasomes and nicotine-induced kidney damage still remains unclear. In the present study, we studied the mechanisms of nicotine-induced nephrotoxicity. We found that nicotine decreased cell viability and induced reactive oxygen species (ROS) generation in human kidney cells. Furthermore, nicotine significantly increased the expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR). Nicotine activated the NLRP6 inflammasome and induced endoplasmic reticulum (ER) stress. Nicotine caused mild apoptosis and necrosis but triggered significant autophagy in human kidney cells. In addition, nicotine induced the NLRP6 inflammasome and autophagy via α7nAChR. In an animal model, the histological analysis in kidney showed evident changes and injury. The results indicated that α7nAChR, IRE1α, LC3 and NLRP6 expression in kidney sections was markedly increased in the nicotine groups. These findings suggest that nicotine causes kidney damage by modulating α7nAChR, NLRP6 inflammasome, ER stress and autophagy.
Highlights
Cigarette smoking is reported to be a common risk factor for various diseases including kidney disease and kidney cancer [1,2,3]
The Cell Viability, reactive oxygen species (ROS) Generation and α7nAChR Expression in Human Kidney Cells Treated with Nicotine
The sulforhodamine B (SRB) assay was performed with human kidney proximal tubular epithelial HK-2 cells and rat renal tubular epithelial NRK-52E cells that were treated with nicotine
Summary
Cigarette smoking is reported to be a common risk factor for various diseases including kidney disease and kidney cancer [1,2,3]. Nicotine is a major component of cigarette smoke and is responsible for the addictive effects of cigarette smoking [4]. Nicotine may affect some biological process such as cell-mediated immunity, apoptosis and angiogenesis by binding to the nicotinic acetylcholine receptors (nAChRs) [5]. Previous studies have demonstrated that nicotine plays a central role in smoking-mediated renal dysfunction [6]. Nicotine caused apoptosis by inducing reactive oxygen species (ROS) generation and cell cycle arrest, and by activating the MAPK and NF-κB signaling pathways in human renal tubular epithelial cells [7]. Some reports have suggested that α7nAChR mediates anti-inflammatory effects through cholinergic modulation [9,10]. The underlying mechanism of α7nAChR in kidney cells is still unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
