10.6084/m9.figshare.5135053.v2
Thakur V.
Thakur
V.
Nargis S.
Nargis
S.
Gonzalez M.
Gonzalez
M.
Pradhan S.
Pradhan
S.
Terreros D.
Terreros
D.
Chattopadhyay M.
Chattopadhyay
M.
Supplementary Material for: Role of Glycyrrhizin in the Reduction of Inflammation in Diabetic Kidney Disease
Karger Publishers
2017
Diabetes
High-mobility group box 1
Inflammation
Toll-like receptor
Glycyrrhizin
Kidney disease
Nuclear factor kappa-B
2017-06-22 06:50:24
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Role_of_Glycyrrhizin_in_the_Reduction_of_Inflammation_in_Diabetic_Kidney_Disease/5135053
<p><b><i>Background:</i></b> Diabetic kidney disease (DKD) is one of the
most debilitating complications of type 2 diabetes. Recent evidence
suggests chronic inflammation to be one of the causal factors of DKD.
The mechanisms entailed are not completely elucidated except that a
variety of cytokines play a major role in this process. High mobility
group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4
(TLR4)-binding cytokine that is involved in inflammation-associated gene
expression. This investigation was designed to assess the involvement
of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD
and to evaluate that whether blocking HMGB1 by its natural inhibitor
Glycyrrhizin (GLC) can reduce the progression of the disease. <b><i>Methods:</i></b>
Studies were carried out in 8-10-weeks old Zucker diabetic fatty (ZDF)
and lean, age- and gender-matched rats. At 10 weeks of age, ZDF rats as
compared to controls, showed hyperglycemia, without proteinuria. After
8-10 weeks of the development of diabetes, ZDF animals that showed
proteinuria were treated with GLC for 4 weeks. In addition, normal rat
kidney (NRK-52E) cells with epithelial-like morphology were
comparatively treated with GLC under hyperglycemic condition in vitro. <b><i>Results:</i></b>
Substantial increase in the expression of HMGB1, TLR4, and NF-κB in
vivo and in vitro under hyperglycemic conditions was observed as
compared to normoglycemic conditions. The overexpression of HMGB1, TLR4,
NF-κB, and glomerular injury marker nestin was significantly
ameliorated by GLC administration. <b><i>Conclusion:</i></b> Our findings suggest that hyperglycemia-induced HMGB1 activation in ZDF rats may contribute to the progression of DKD.</p>