Activation of PPARγ attenuates LPS-induced acute lung injury by inhibition of HMGB1-RAGE levels.
HMGB1-RAGE signaling pathway is involved in the development of ALI/ARDS. At the same time, activation of PPARγ has been shown to inhibit the occurrence of ALI/ARDS. However, it is unknown whether activation of PPARγ benefits ALI/ARDS by regulation of HMGB1-RAGE signaling. This study aims to address these issues. We found in this study that LPS induced dramatic pathological changes of ALI in mice; these were accompanied with elevated expression of HMGB1 and RAGE. Prior treatment of mice with PPARγ agonist rosiglitazone significantly suppressed LPS-induced ALI and reversed the elevation of HMGB1 and RAGE; these were accompanied with the induction of HO-1. The presence of selective HO-1 inhibitor Znpp abolished the protective effects of rosiglitazone on LPS-induced ALI. This study suggests that activation of PPARγ inhibits the development of LPS-induced ALI by negative modulation of HMGB1-RAGE pathway, and has a potential value in the clinical treatment of such conditions.
Guizuo
G
Wang
Lu
L
Liu
Yonghong
Y
Zhang
Dong
D
Han
Jiamei
J
Liu
Jing
J
Xu
Xinming
X
Xie
Yuanyuan
Y
Wu
Dexin
D
Zhang
Rui
R
Ke
Shaojun
S
Li
Yanting
Y
Zhu
Wei
W
Feng
Manxiang
M
Li
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051547:Heme Oxygenase-1