Proposed mechanism underlying the GW501516-mediated anti-inflammatory effect in proximal tubular cells in proteinuric kidney diseases.
- Xu Yang (112496)
- Shinji Kume (343585)
- Yuki Tanaka (112000)
- Keiji Isshiki (343586)
- Shin-ichi Araki (103039)
- Masami Chin-Kanasaki (343587)
- Toshiro Sugimoto (343588)
- Daisuke Koya (343589)
- Masakazu Haneda (343591)
- Takeshi Sugaya (343594)
- Detian Li (343596)
- Ping Han (150906)
- Yoshihiko Nishio (343600)
- Atsunori Kashiwagi (131444)
- Hiroshi Maegawa (103055)
- Takashi Uzu (103045)
Publication date
February 2013
DOIAbstract
<p>Both TNFα and palmitate induce the phosphorylation of TAK1 in a receptor dependent manner. The phosphorylation of TAK1 activates the NFκB pathway via degradation of IκB. The p65 subunit of NFκB translocates into the nucleus, upregulates the transcription of the pro-inflammatory gene, <i>MCP-1</i>, and causes inflammation. GW501516 can inhibit the phosphorylation of TAK1, but not of MAPKs (including ERK), and the activation of the NFκB-associated inflammatory response in proximal tubular cells. TNFα: tumor necrotic factor α; TNFR: TNFα receptor; TLR4: toll-like receptor 4; IKK: IκB Kinase; FFA: free fatty acid; MCP-1: monocyte chemoattractant protein-1.</p
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