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Contribution of High Mobility Group Box 1 to Nicotine‐Induced Podocyte Injury
Author(s) -
Boini Krishna M,
Patibandla Sai,
Singh Gurinder Bir,
Puchchakayala Goverdhan,
Koka Saisudha
Publication year - 2019
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.2019.33.1_supplement.572.3
Subject(s) - podocin , hmgb1 , podocyte , western blot , nicotine , tlr4 , pharmacology , inflammation , medicine , chemistry , high mobility group , immunofluorescence , microbiology and biotechnology , biology , immunology , kidney , biochemistry , antibody , proteinuria , gene
High mobility group box 1 protein (HMGB1), a nuclear DNA binding protein is released under pathological conditions and locally act as one of the potent damage‐associated molecular patterns (DAMPs) to produce tissue injury and chronic inflammation. However, it remains unknown whether HMGB1 is implicated in nicotine‐induced podocyte injury. In the present study, we found that nicotine dose‐dependently increased the production of HMGB1 in cultured podocytes, and that HMGB1 binder and inhibitor, glycyrrhizin (Gly) completely blocked its release induced by nicotine. Immunofluorescence and western blot analysis showed that nicotine treatment significantly decreased the podocin expression compared to control cells. However, prior treatment with Gly attenuated the nicotine‐induced podocin reduction. Furthermore, western blot analysis showed that nicotine treatment significantly increased the TLR4 expression compared to control cells but not in Gly treated cells. In addition, prior treatment with TLR4 siRNA transfection significantly attenuated the nicotine‐induced podocin reduction in podocytes. Based on these results, it is concluded that HMGB1 is one of important mediators of nicotine‐induced podocyte injury. HMGB1 may be a therapeutic target for treatment or prevention of glomerulosclerosis associated with smoking. Support or Funding Information National Institutes of Health (DK104031) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .