{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:11Z","timestamp":1786602431421,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Nicotine has been shown to induce Nlrp3 (nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome activation, thereby contributing to podocyte injury. However, the molecular mechanisms underlying nicotine-induced Nlrp3 inflammasome activation and subsequent podocyte dysfunction remain largely unknown. The present study investigated whether membrane raft (MR)-associated redox signalling plays a critical role in nicotine-induced Nlrp3 inflammasome activation and podocyte injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Nicotine treatment induced membrane raft clustering in podocytes in a dose-dependent manner. Upon nicotine stimulation, the NADPH oxidase subunits gp91\n                      <jats:sup>phox<\/jats:sup>\n                      and p47\n                      <jats:sup>phox<\/jats:sup>\n                      were recruited and aggregated within membrane raft clusters, leading to the formation of a membrane raft redox signalling platform. The formation of this signalling platform was significantly inhibited by pretreatment with the membrane raft disruptor methyl-\u03b2-cyclodextrin (MCD), the NADPH oxidase inhibitor diphenyleneiodonium (DPI), or the acid sphingomyelinase (Asm) inhibitor amitriptyline. Nicotine also markedly enhanced the colocalization of Nlrp3 with ASC and caspase-1, indicating inflammasome assembly, and significantly increased caspase-1 activity, IL-1\u03b2 production, desmin expression, podocyte permeability, and apoptosis compared with control cells. These effects were significantly attenuated by pretreatment with MCD, DPI, the caspase-1 inhibitor WEHD, or amitriptyline. Furthermore, immunofluorescence analysis demonstrated that nicotine significantly reduced podocin expression, whereas pretreatment with MCD, DPI, WEHD, or amitriptyline largely preserved podocin expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that membrane raft-associated redox signalling serves as a critical upstream mechanism driving nicotine-induced NLRP3 inflammasome activation and podocyte injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1916699","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:32:59Z","timestamp":1786599179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel redox signalling axis mediates nicotine-induced podocyte injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohammad Atiqur","family":"Rahman","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishith","family":"Yellu","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varnika","family":"Pavirala","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayantap","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saisudha","family":"Koka","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna M.","family":"Boini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1089\/ars.2014.5994","article-title":"Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?","volume":"22","author":"Abais","year":"2015","journal-title":"Antioxid. 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