Table 1.
PPAR ligands | PPAR types | Possible involved HMGB1 signaling or expression | Effects on biological actions of HMGB1 | Cell lines | Animal model | Potential applied diseases | References |
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EPA | PPAR-γ | HMGB1/TLR9 signaling | EPA inhibits HMGB1/TLR9 pathway and downregulates HMGB1 expression in brain cortex. | — | Ovariectomized rat model of cerebral ischemia | Ischemic brain damage and ischemic stroke | [39] |
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Telmisartan | PPAR-γ | — | Telmisartan decreases plasma HMGB1 levels and suppresses the expression of HMGB1 in macrophages or microglial cells. | — | Mice model of focal cerebral ischemia | Postischemic injury | [38] |
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Troglitazone | PPAR-γ | Transcriptional activity of HMGB1 promoter and NF-κB or AP-1 signaling | Troglitazone inhibits HMGB1 expression in endothelial cells. | Vascular endothelial cells | — | Sepsis, arthritis, and atherosclerosis | [41] |
miRNA-based regulation | Troglitazone inhibits HMGB1 expression through upregulation of miR-142-3p. | THP-1 cells | Mice model of endotoxemia | Sepsis | [42] | ||
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Rosiglitazone | PPAR-γ | HMGB1/TLR4 signaling | Rosiglitazone decreases LPS-induced plasma HMGB1 levels and inhibits HMGB1 release of RAW264.7 cells. | RAW264.7 cells | Mice model of endotoxemia | Sepsis | [43] |
HMGB1/RAGE signaling | Rosiglitazone reverses LPS-induced elevation of HMGB1 in bronchoalveolar lavage fluid. | — | Mice model of ALI | ALI and ARDS | [44, 45] | ||
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Pioglitazone | PPAR-γ | HMGB1/TLR4 and HMGB1/RAGE signaling | Pioglitazone reverses AGEs-induced elevation of HMGB1 expression in OA chondrocytes. | Chondrocytes | — | OA | [46] |
HMGB1/RAGE signaling | Pioglitazone downregulates HMGB1 expression and inhibits HMGB1/RAGE signaling in HCC cells. | SMMC-7721 and HepG2 cells | — | Hepatocellular carcinoma | [47] | ||
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Fenofibrate | PPAR-α | — | Fenofibrate reverses basal and LPS-induced HMGB1 expression, as well as modulating its cellular localization. | Cardiomyocytes | Mice model of hypertrophic myocardium | Cardiac hypertrophy | [48] |
EPA: eicosapentaenoic acid; LPS: lipopolysaccharide; TLR: Toll-like receptor; RAGE: receptor for advanced glycation end-products; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; AGEs: advanced glycation end-products; OA: osteoarthritis; HCC: hepatocellular carcinoma.