Premium
Contribution of High Mobility Group Box 1 to Obesity‐Induced Podocyte Dysfunction and Glomerular Injury
Author(s) -
Koka Saisudha,
Mohammad Razia S.,
Singh Gurinder Bir,
Kshirasagar Naresh,
Hussain Tahir,
Li Ningjun,
Li PinLan,
Li Xiang,
Boini Krishna M.
Publication year - 2018
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.2018.32.1_supplement.562.7
Subject(s) - podocyte , podocin , hmgb1 , medicine , endocrinology , glycyrrhizin , western blot , tlr4 , inflammation , adipokine , chemistry , diabetes mellitus , insulin resistance , kidney , biochemistry , 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 potent damage‐associated molecular patterns (DAMPs) to produce tissue injury and chronic inflammation. However, it remains unknown whether HMGB1 is implicated in obesity‐induced podocyte injury. In the present study, we found that obesity‐induced adipokine visfatin dose‐dependently increased the production of HMGB1 in cultured podocytes compared to control cells. However, pretreatment with HMGB1 binder, glycyrrhizin (Gly) completely blocked HMGB1 release which was induced by visfatin. Further, immunofluorescence analysis showed that visfatin treatment significantly decreased the podocin expression (podocyte damage) compared to control cells. However, prior treatment with glycerrhizin attenuated the visfatin‐induced podocin reduction. Furthermore, glycyrrhizin treatment was found to preserve podocyte morphology by maintaining the distinct arrangement of F‐actin fibers normally lost in response to visfatin. It also prevented podocyte dysfunction by restoring visfatin‐induced suppression of VEGF production and secretion. In addition, functional studies showed that dextran flux was significantly increased in visfatin treated podocytes compared to control cells. This visfatin‐induced increase in permeability was markedly reduced in the presence of glycyrrhizin. In in vivo studies, C57BL6 mice were fed with high fat diet or normal chow for 14 weeks to produce obesity. Western blot analysis showed that high fat diet treatment significantly increased the HMGB1, TLR4 and RAGE expression in glomeruli of high fat diet fed mice compared to normal diet fed mice. However, such increase of HMGB1, TLR4 and RAGE expression were attenuated in glomeruli of glycyrrhizin treated mice. Based on these results, it is concluded that HMGB1 is one of important mediators of obesity‐induced podocyte injury and glomerular sclerosis. HMGB1 may be a therapeutic target for treatment or prevention of glomerulosclerosis associated with obesity. Support or Funding Information supported by NIH grant, DK104031 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .