TY - JOUR
T1 - Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor
AU - Zheng, Cai Mei
AU - Lee, Yu Hsuan
AU - Chiu, I. Jen
AU - Chiu, Yu Jhe
AU - Sung, Li Chin
AU - Hsu, Yung Ho
AU - Chiu, Hui Wen
N1 - Funding Information:
This study was supported by the Taipei Medical University-Shuang Ho Hospital (107TMU-SHH-01), the Ministry of Science and Technology, Taiwan (MOST 108-2314-B-038-044, MOST 108-2314-B-039-061-MY3 and MOST 109-2314-B-038 -078 -MY3) and China Medical University, Taichung, Taiwan (CMU109-MF-25).
Funding Information:
funding acquisition, C.-M.Z., Y.-H.L., L.-C.S., Y.-H.H. and H.-W.C.; investigation, Y.-J.C. and H.-W.C.; methodology, C.-M.Z., Y.-H.L., I.-J.C., Y.-J.C. and L.-C.S.; supervision, Y.-H.H. and H.-W.C.; writing—original draft, C.-M.Z., L.-C.S., Y.-H.H. and H.-W.C.; writing—review and editing, Y.-H.H. and H.-W.C. All authors have read and agreed draft, C.-M.Z., L.-C.S., Y.-H.H. and H.-W.C.; writing—review and editing, Y.-H.H. and H.-W.C. All authors have read and agreed to the published version of the manuscript. Funding: This study was supported by the Taipei Medical University-Shuang Ho Hospital (107TMU-SHH-01), thFeunMdiinnigst:rTyhoifs Ssctuiednyc ewaansd sTuepcphonrotelodg by,yT tahiwe Tanai(pMeiO MSTed1i0c8a-l 2U31n4iv-Be-r0s3it8y--0S4h4u, aMnOg SHTo1 H08o-s2p3i1t4a-lB (-100379T-0M6U1--MSHY3Ha-0n1d), the Ministry of Science and Technology, Taiwan (MOST 108-2314-B-038-044, MOST 108-2314-B-039-061-MY3 and MOST 109-2314-B-038 -078 -MY3) and China Medical University, Taichung, Taiwan (CMU109-MF-25). (rat renal tubular cell line) were obtained from Cheng-Hsien Chen (Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan). Experiments and data analysis were performed in part through the use of the Medical Research Core Facilities Center, Office of Research & Development at China Medical University, Taichung, Taiwan.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Alpha7 nicotinic acetylcholine receptor
KW - Autophagy
KW - Endoplasmic reticulum stress
KW - Nicotine
KW - NLRP6 inflammasome
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UR - http://www.scopus.com/inward/citedby.url?scp=85094608908&partnerID=8YFLogxK
U2 - 10.3390/toxics8040092
DO - 10.3390/toxics8040092
M3 - Article
AN - SCOPUS:85094608908
SN - 2305-6304
VL - 8
SP - 1
EP - 16
JO - Toxics
JF - Toxics
IS - 4
M1 - 92
ER -
