Author:
Kono Keiichi,Kamijo Yuji,Hora Kazuhiko,Takahashi Kyoko,Higuchi Makoto,Kiyosawa Kendo,Shigematsu Hidekazu,Gonzalez Frank J.,Aoyama Toshifumi
Abstract
The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor α (PPARα) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPARα in mesangial cells, wild-type and Ppara-null cultured mesangial cells were exposed to lipopolysaccharide (LPS). LPS treatment caused enhanced proinflammatory responses in the Ppara-null cells compared with wild-type cells, as revealed by the induction of interleukin-6, enhanced cell proliferation, and the activation of the nuclear factor (NF)-κB signaling pathway. In wild-type cells resistant to inflammation, constitutive expression of PPARα was undetectable. However, LPS treatment induced the significant appearance and substantial activation of PPARα, which would attenuate the proinflammatory responses through its antagonizing effects on the NF-κB signaling pathway. The induction of PPARα was coincident with the appearance of α-smooth muscle actin, which might be associated with the phenotypic changes of mesangial cells. Moreover, another examination using LPS-injected wild-type mice demonstrated the appearance of PPARα-positive cells in glomeruli, suggesting in vivo correlation with PPARα induction. These results suggest that PPARα plays crucial roles in the attenuation of inflammatory response in activated mesangial cells. PPARα might be a novel therapeutic target against glomerular diseases.
Publisher
American Physiological Society
Cited by
43 articles.
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