{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:58:26Z","timestamp":1792807106099,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Medical University-Shuang Ho Hospital","award":["107TMU-SHH-01"],"award-info":[{"award-number":["107TMU-SHH-01"]}],"id":[{"id":"https:\/\/ror.org\/04k9dce70","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2314-B-038-044"],"award-info":[{"award-number":["MOST 108-2314-B-038-044"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2314-B-039-061-MY3"],"award-info":[{"award-number":["MOST 108-2314-B-039-061-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-038 -078 -MY3"],"award-info":[{"award-number":["MOST 109-2314-B-038 -078 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>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 (\u03b17nAChR). 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 \u03b17nAChR. In an animal model, the histological analysis in kidney showed evident changes and injury. The results indicated that \u03b17nAChR, IRE1\u03b1, LC3 and NLRP6 expression in kidney sections was markedly increased in the nicotine groups. These findings suggest that nicotine causes kidney damage by modulating \u03b17nAChR, NLRP6 inflammasome, ER stress and autophagy.<\/jats:p>","DOI":"10.3390\/toxics8040092","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T10:38:35Z","timestamp":1603708715000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Nicotine Causes Nephrotoxicity through the Induction of NLRP6 Inflammasome and Alpha7 Nicotinic Acetylcholine Receptor"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3951","authenticated-orcid":false,"given":"Cai-Mei","family":"Zheng","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7660-3770","authenticated-orcid":false,"given":"Yu-Hsuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutics, China Medical University, Taichung 40604, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Jen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jhe","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-5592","authenticated-orcid":false,"given":"Li-Chin","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Ho","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-390X","authenticated-orcid":false,"given":"Hui-Wen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nrurol.2010.46","article-title":"Epidemiology and risk factors for kidney cancer","volume":"7","author":"Chow","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/01902148.2018.1556748","article-title":"Hypermethylation of mitochondrial transcription factor A induced by cigarette smoke is associated with chronic obstructive pulmonary disease","volume":"45","author":"Peng","year":"2019","journal-title":"Exp. Lung Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.bcp.2013.07.014","article-title":"Nicotine signaling and progression of chronic kidney disease in smokers","volume":"86","author":"Jain","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/382255a0","article-title":"Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs","volume":"382","author":"Pontieri","year":"1996","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1007\/s10495-007-0102-8","article-title":"Nicotine and apoptosis","volume":"12","author":"Zeidler","year":"2007","journal-title":"Apoptosis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000163593","article-title":"Nicotine augments glomerular injury in a rat model of acute nephritis","volume":"29","author":"Jaimes","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, C.S., Choi, J.S., Joo, S.Y., Bae, E.H., Ma, S.K., Lee, J., and Kim, S.W. (2016). Nicotine-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152591"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0896-6273(90)90344-F","article-title":"A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX","volume":"5","author":"Couturier","year":"1990","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature01339","article-title":"Nicotinic acetylcholine receptor alpha 7 subunit is an essential regulator of inflammation","volume":"421","author":"Wang","year":"2003","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2017.05.002","article-title":"Cholinergic modulation of the immune system presents new approaches for treating inflammation","volume":"179","author":"Hoover","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/apha.12861","article-title":"Vagal nerve stimulation reduces infarct size via a mechanism involving the alpha-7 nicotinic acetylcholine receptor and downregulation of cardiac and vascular arginase","volume":"221","author":"Kiss","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41581-019-0158-z","article-title":"The role of inflammasomes in kidney disease","volume":"15","author":"Komada","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"188","DOI":"10.2119\/molmed.2017.00077","article-title":"Inflammasome and autophagy regulation\u2014A two-way street","volume":"23","author":"Sun","year":"2017","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2019.01.014","article-title":"Multifactorial functions of the inflammasome component NLRP3 in pathogenesis of chronic kidney diseases","volume":"96","author":"Mulay","year":"2019","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41419-019-1356-0","article-title":"Autophagy attenuates tubulointerstital fibrosis through regulating transforming growth factor-beta and NLRP3 inflammasome signaling pathway","volume":"10","author":"Nam","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.2217\/nnm-2017-0256","article-title":"Resveratrol-loaded nanoparticles conjugated with kidney injury molecule-1 as a drug delivery system for potential use in chronic kidney disease","volume":"12","author":"Lin","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41419-017-0257-3","article-title":"Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis","volume":"9","author":"Wu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7187","DOI":"10.4049\/jimmunol.1100412","article-title":"A functional role for Nlrp6 in intestinal inflammation and tumorigenesis","volume":"186","author":"Chen","year":"2011","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1080\/15548627.2016.1190071","article-title":"Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2\/M arrest and renal fibrosis","volume":"12","author":"Li","year":"2016","journal-title":"Autophagy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101254","DOI":"10.1016\/j.redox.2019.101254","article-title":"PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation","volume":"26","author":"Lin","year":"2019","journal-title":"Redox Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2019.02.008","article-title":"Nicotine-mediated autophagy of vascular smooth muscle cell accelerates atherosclerosis via nAChRs\/ROS\/NF-\u03baB signaling pathway","volume":"284","author":"Wang","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/ncb0805-766","article-title":"ERAD: The long road to destruction","volume":"7","author":"Meusser","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fphys.2017.00074","article-title":"Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease","volume":"8","author":"Maekawa","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1172\/JCI40027","article-title":"The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5","volume":"120","author":"Rouschop","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/EBC20170092","article-title":"ER homeostasis and autophagy","volume":"61","author":"Smith","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/toxsci\/kfw019","article-title":"Nicotine Directly Induces Endoplasmic Reticulum Stress Response in Rat Placental Trophoblast Giant Cells","volume":"151","author":"Wong","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1210\/en.2013-1839","article-title":"Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats","volume":"155","author":"Nogueiras","year":"2014","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2353\/ajpath.2007.070188","article-title":"Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability","volume":"171","author":"Ding","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_32","first-page":"119","article-title":"Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: Preparation, in vitro and ex vivo evaluation","volume":"6","author":"Saremi","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/cns.12758","article-title":"Activating \u03b17 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of \u03b2-arrestin-1","volume":"23","author":"Ke","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/ajkd.2002.34487","article-title":"Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis","volume":"40","author":"Dharnidharka","year":"2002","journal-title":"Am. J. Kidney Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.pharmtox.48.113006.094615","article-title":"Biomarkers of acute kidney injury","volume":"48","author":"Vaidya","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2215\/CJN.03740907","article-title":"Smoking: A risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients--absence of evidence or evidence of absence?","volume":"3","author":"Orth","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1681\/ASN.2005091012","article-title":"Association of single measurements of dipstick proteinuria, estimated glomerular filtration rate, and hematocrit with 25-year incidence of end-stage renal disease in the multiple risk factor intervention trial","volume":"17","author":"Ishani","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1600-0668.2005.00330.x","article-title":"A study of reactive oxygen species in mainstream of cigarette","volume":"15","author":"Huang","year":"2005","journal-title":"Indoor Air"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0013-9351(05)80143-4","article-title":"Cadmium determination in Mexican-produced tobacco","volume":"55","author":"Saldivar","year":"1991","journal-title":"Environ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/tc.12.4.424","article-title":"Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke","volume":"12","author":"Fowles","year":"2003","journal-title":"Tob. Control"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30422","DOI":"10.1074\/jbc.M504688200","article-title":"Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation","volume":"280","author":"Guo","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H76","DOI":"10.1152\/ajpheart.00693.2006","article-title":"Nicotine: The link between cigarette smoking and the progression of renal injury?","volume":"292","author":"Jaimes","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8015","DOI":"10.1073\/pnas.120055097","article-title":"Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db\/db diabetic mice","volume":"97","author":"Ziyadeh","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s004670000461","article-title":"Molecular basis of renal fibrosis","volume":"15","author":"Eddy","year":"2000","journal-title":"Pediatric Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1124\/mol.116.104240","article-title":"Understanding the Bases of Function and Modulation of \u03b17 Nicotinic Receptors: Implications for Drug Discovery","volume":"90","author":"Corradi","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1089\/ars.2007.1782","article-title":"Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword?","volume":"9","author":"Malhotra","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wong, M.K., Nicholson, C.J., Holloway, A.C., and Hardy, D.B. (2015). Maternal nicotine exposure leads to impaired disulfide bond formation and augmented endoplasmic reticulum stress in the rat placenta. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122295"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2119\/molmed.2013.00117","article-title":"\u03b17 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release","volume":"20","author":"Lu","year":"2014","journal-title":"Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.3389\/fimmu.2018.01604","article-title":"C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation","volume":"9","author":"Richter","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2183026","DOI":"10.1155\/2016\/2183026","article-title":"ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia\/Reperfusion Injury","volume":"2016","author":"Minutoli","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.biopha.2018.05.007","article-title":"Autophagy in health and disease: A comprehensive review","volume":"104","author":"Saha","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1152\/physrev.00030.2009","article-title":"Regulation of mammalian autophagy in physiology and pathophysiology","volume":"90","author":"Ravikumar","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/ki.2012.261","article-title":"Autophagy in proximal tubules protects against acute kidney injury","volume":"82","author":"Jiang","year":"2012","journal-title":"Kidney Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/ki.2012.337","article-title":"Autophagy protects proximal tubular cells from injury and apoptosis","volume":"82","author":"Kaushal","year":"2012","journal-title":"Kidney Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108943","DOI":"10.1016\/j.cbi.2020.108943","article-title":"Nicotine-induced autophagy via AMPK\/mTOR pathway exerts protective effect in colitis mouse model","volume":"317","author":"Gao","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.bbrc.2019.11.086","article-title":"Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression","volume":"522","author":"Xing","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/8\/4\/92\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:07Z","timestamp":1760178487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/8\/4\/92"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["toxics8040092"],"URL":"https:\/\/doi.org\/10.3390\/toxics8040092","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,26]]}}}