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Article

Nicotine Causes Nephrotoxicity through the Induction of NLRP6 Inflammasome and Alpha7 Nicotinic Acetylcholine Receptor

by 1,2,3,†, 4, 2,3,5, 2,5, 6,7,8,†, 1,2,3,* and 2,3,5,*
1
Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
2
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
3
TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan
4
Department of Cosmeceutics, China Medical University, Taichung 40604, Taiwan
5
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
6
Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
7
Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
8
Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxics 2020, 8(4), 92; https://doi.org/10.3390/toxics8040092
Received: 29 July 2020 / Revised: 16 October 2020 / Accepted: 20 October 2020 / Published: 26 October 2020
(This article belongs to the Section Toxicology)
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. View Full-Text
Keywords: nicotine; alpha7 nicotinic acetylcholine receptor; NLRP6 inflammasome; autophagy; endoplasmic reticulum stress nicotine; alpha7 nicotinic acetylcholine receptor; NLRP6 inflammasome; autophagy; endoplasmic reticulum stress
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MDPI and ACS Style

Zheng, C.-M.; Lee, Y.-H.; Chiu, I.-J.; Chiu, Y.-J.; Sung, L.-C.; Hsu, Y.-H.; Chiu, H.-W. Nicotine Causes Nephrotoxicity through the Induction of NLRP6 Inflammasome and Alpha7 Nicotinic Acetylcholine Receptor. Toxics 2020, 8, 92. https://doi.org/10.3390/toxics8040092

AMA Style

Zheng C-M, Lee Y-H, Chiu I-J, Chiu Y-J, Sung L-C, Hsu Y-H, Chiu H-W. Nicotine Causes Nephrotoxicity through the Induction of NLRP6 Inflammasome and Alpha7 Nicotinic Acetylcholine Receptor. Toxics. 2020; 8(4):92. https://doi.org/10.3390/toxics8040092

Chicago/Turabian Style

Zheng, Cai-Mei, Yu-Hsuan Lee, I-Jen Chiu, Yu-Jhe Chiu, Li-Chin Sung, Yung-Ho Hsu, and Hui-Wen Chiu. 2020. "Nicotine Causes Nephrotoxicity through the Induction of NLRP6 Inflammasome and Alpha7 Nicotinic Acetylcholine Receptor" Toxics 8, no. 4: 92. https://doi.org/10.3390/toxics8040092

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