| RRC ID |
74088
|
| 著者 |
Arimura N, Watanabe H, Kato H, Imafuku T, Nakano T, Sueyoshi M, Chikamatsu M, Tokumaru K, Nagasaki T, Maeda H, Tanaka M, Matsushita K, Maruyama T.
|
| タイトル |
Advanced Oxidation Protein Products Contribute to Chronic-Kidney-Disease-Induced Adipose Inflammation through Macrophage Activation.
|
| ジャーナル |
Toxins (Basel)
|
| Abstract |
Fat atrophy and adipose tissue inflammation can cause the pathogenesis of metabolic symptoms in chronic kidney disease (CKD). During CKD, the serum levels of advanced oxidation protein products (AOPPs) are elevated. However, the relationship between fat atrophy/adipose tissue inflammation and AOPPs has remained unknown. The purpose of this study was to investigate the involvement of AOPPs, which are known as uremic toxins, in adipose tissue inflammation and to establish the underlying molecular mechanism. In vitro studies involved co-culturing mouse-derived adipocytes (differentiated 3T3-L1) and macrophages (RAW264.7). In vivo studies were performed using adenine-induced CKD mice and AOPP-overloaded mice. Fat atrophy, macrophage infiltration and increased AOPP activity in adipose tissue were identified in adenine-induced CKD mice. AOPPs induced MCP-1 expression in differentiated 3T3-L1 adipocytes via ROS production. However, AOPP-induced ROS production was suppressed by the presence of NADPH oxidase inhibitors and the scavengers of mitochondria-derived ROS. A co-culturing system showed AOPPs induced macrophage migration to adipocytes. AOPPs also up-regulated TNF-α expression by polarizing macrophages to an M1-type polarity, and then induced macrophage-mediated adipose inflammation. In vitro data was supported by experiments using AOPP-overloaded mice. AOPPs contribute to macrophage-mediated adipose inflammation and constitute a potential new therapeutic target for adipose inflammation associated with CKD.
|
| 巻・号 |
15(3)
|
| 公開日 |
2023-2-26
|
| DOI |
10.3390/toxins15030179
|
| PII |
toxins15030179
|
| PMID |
36977070
|
| PMC |
PMC10059001
|
| MeSH |
Advanced Oxidation Protein Products*
Animals
Inflammation / metabolism
Kidney / metabolism
Macrophage Activation
Mice
Obesity
Reactive Oxygen Species / metabolism
Renal Insufficiency, Chronic* / metabolism
|
| IF |
3.531
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
