Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor

Cai Mei Zheng; Yu Hsuan Lee; I. Jen Chiu; Yu Jhe Chiu; Li Chin Sung; Yung Ho Hsu; Hui Wen Chiu

doi:10.3390/toxics8040092

Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor

Cai Mei Zheng, Yu Hsuan Lee, I. Jen Chiu, Yu Jhe Chiu, Li Chin Sung, Yung Ho Hsu, Hui Wen Chiu

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

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.

Original language	English
Article number	92
Pages (from-to)	1-16
Number of pages	16
Journal	Toxics
Volume	8
Issue number	4
DOIs	https://doi.org/10.3390/toxics8040092
Publication status	Published - Dec 2020

Keywords

Alpha7 nicotinic acetylcholine receptor
Autophagy
Endoplasmic reticulum stress
Nicotine
NLRP6 inflammasome

ASJC Scopus subject areas

Toxicology
Health, Toxicology and Mutagenesis
Chemical Health and Safety

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/toxics8040092

Cite this

@article{e38a09bd5de744ebb19088ef728cec37,

title = "Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor",

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.",

keywords = "Alpha7 nicotinic acetylcholine receptor, Autophagy, Endoplasmic reticulum stress, Nicotine, NLRP6 inflammasome",

author = "Zheng, {Cai Mei} and Lee, {Yu Hsuan} and Chiu, {I. Jen} and Chiu, {Yu Jhe} and Sung, {Li Chin} and Hsu, {Yung Ho} and Chiu, {Hui Wen}",

note = "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: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = dec,

doi = "10.3390/toxics8040092",

language = "English",

volume = "8",

pages = "1--16",

journal = "Toxics",

issn = "2305-6304",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

}

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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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 -

Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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