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Nicotine‐Induced Glomerular Injury is Ameliorated in NLRP3 Gene Knockout Mice
Author(s) -
Puchchakayala Goverdhan,
Li Xiang,
Koka Saisudha,
Boini Krishna M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08679
Subject(s) - nicotine , inflammasome , knockout mouse , podocyte , podocin , medicine , nephrin , endocrinology , pharmacology , kidney , receptor , proteinuria
Nicotine, a major compound of tobacco and the key component of the vapor inhaled via electronic cigarettes, has been shown to worsen kidney injury in animal models of acute kidney injury, diabetes, subtotal nephrectomy. However, it remains unknown how nicotine‐induced glomerular injury. Hence, the present study tested whether NLRP3 inflammasome mediates the nicotine‐induced glomerular injury. Uninephrectomized Nlrp3 knockout (Nlrp3 −/− ) and wild type (Nlrp3 +/+ ) mice were fed a normal chow for 5 weeks with or without nicotine treatment to produce glomerular injury. Nicotine treatment significantly increased the colocalization of Nlrp3 (Nod‐like receptor protein 3) with ASC (apoptosis‐associated speck‐like protein) or Caspase‐1 in glomeruli of Nlrp3 +/+ mice than in vehicle treated mice. However, such nicotine‐induced increases in colocalization of Nlrp3 with ASC or Caspase‐1 was attenuated in Nlrp3 −/− mice. In consistency with decreased inflammasome formation, the caspase‐1 activity and IL‐1β production was significantly attenuated in glomeruli of Nlrp3 −/− mice. Morphological examinations showed that nicotine‐induced profound injury in glomeruli of Nlrp3 +/+ mice which was markedly attenuated in Nlrp3 −/− mice. The decreased glomerular damage index in Nlrp3 −/− mice was accompanied by attenuated proteinuria. Immunofluorescence analysis showed that the nicotine treatment significantly decreased the expression of podocin but increased desmin levels in glomeruli from Nlrp3 +/+ mice but not in those from Nlrp3−/− mice. Furthermore the nicotine‐induced hypertension was significantly attenuated in Nlrp3 −/− mice. In conclusion, these observations disclose a pivotal role of Nlrp3 inflammasomes in mediating the glomerular sclerosis associated with smoking. Support or Funding Information R01DK104031 and R56HL143809